DolceraWiki - User contributions [en]

File:Comparative toxicogenomics1.jpg

2009-11-19T14:37:30Z

Tony.kurian@dolcera.com:

File:Toxicology1.jpg

2009-11-19T14:37:25Z

Tony.kurian@dolcera.com:

Toxicology

2009-11-18T15:57:37Z

Tony.kurian@dolcera.com:

[[Image:Toxicology1.jpg|right|400 px|Toxicology]]

==Introduction==
*'''Toxicology''' is the science that investigates the adverse effects of chemicals on health.
*It describes the relationship of the body’s response to different amounts of an agent such as a drug or toxin
*Routes of Entry : Ingestion,Inhalation,Dermal absorption,Ocular, etc.,
*Bio-monitoring is done for some toxic exposures such as blood lead levels or metabolites of chemicals (biomarkers).
*Threshold levels refers to the amount of a substance necessary to cause a response in the body.
*Toxicity can be generally broken down into two categories:
**'''Acute toxicity''' refers to the rapid development of symptoms/effects after the intake of relatively high doses of the toxicant.Acute toxicity refers to immediate harmful effects generated by sufficiently large doses.
**'''Chronic toxicity''' refers to the harmful effects of long-term exposure to relatively low doses of toxicant. This would include traces of pesticides in foods, air pollution, etc.A single compound may generate both acute and chronic toxic effects depending on the dose and duration of exposure.
*Drugs are taken voluntarily and often under the supervision of a licensed health care provider.Hazardous chemical exposures are most often involuntary.
*Host factors may impact the therapeutic or toxic effect of a drug or chemical.Age,Genetics,Weight,Drugs that a person may be taking,Pregnancy status and others
*The scientific pursuit of toxicology is typically divided between '''Observational studies''' looking at what effects result from exposure to a particular substance and '''Mechanistic studies''' which attempt to understand and explain the basis for such effects.These two activities form the basis of toxicology

==Branches of Toxicology==
*'''Clinical toxicology'''Involves the application of toxicological principles within a diagnostic setting, usually to determine whether a presenting adverse effect or disease or injury is due to some type of chemical exposure. This area of toxicology is typically practiced by a physician, nurse or other clinician, often times in consultation with the experimental toxicologist, who is in a position to better explain certain published experimental findings and whether they would be applicable to the case at hand.
*'''Regulatory toxicology'''- Relies on risk assessment and experimental data to determine the risk and benefits, or the costs and benefits of exposure to certain chemicals, to determine whether such chemical will be allowed in the public sphere and to what extent its use and exposure will be regulated. This field of toxicology probably has the greatest effect on our daily lives of all the different fields of toxicology. Deciphers and analyzes toxicological data for risk estimation, Solvent vapor thresholds in industry and Safe level for human drugs
*'''Biochemical and Molecular Toxicology'''- Determining mode of action of chemicals at the molecular level , Effect of chemicals on DNA,Cancer genes
*'''Product Development Toxicology''' - Service and pre-clinical toxicology for product development, Evaluation of full toxic potential of chemicals destined for drug use and Establishing safe dose for people
*'''Risk assessment''' - Determining probabilistically, outside the laboratory, the likelihood of an adverse effect based on a particular exposure scenario. This is not experimental activity, involves much more uncertainty about its findings and is as much art as science. It is conducted quantitatively, relying on mathematics and computer modeling, or qualitatively, relying more on experience and similar scenarios that have been previously looked at. [http://www.google.co.in/url?sa=t&source=web&ct=res&cd=1&ved=0CAcQFjAA&url=http%3A%2F%2Fnursingworld.org%2Fmods%2Fmod449%2Fsattler.ppt&ei=tcMDS9q-IJbs6gO1vu1_&usg=AFQjCNFCRONmZmVDmRE0tg1InTvr0UirLA&sig2=npkqa2dcwOWpV7LcEOChVg Source]

==Comparative Toxicogenomics==
[[Image:Comparative toxicogenomics1.jpg|right|450 px|Comparative Toxicogenomics]]

*It describes the relationships between Drugs,genes and human diseases.

*To study the effects of environmental chemicals on human health.

*The etiology of many chronic diseases involves interactions between environmental factors and genes that modulate important physiological processes. Chemicals are an important component of the environment. Conditions such as asthma, cancer, diabetes, hypertension, immunodeficiency, and Parkinson's disease are known to be influenced by the environment; however, the molecular mechanisms underlying these correlations are not well understood. Comparative Toxicogenomics database may help resolve these mechanisms.[http://ctd.mdibl.org/ Source]

==Databases==
*[http://www.ngvl.org/include/tox/index.php National Gene Vector Laboratories (NGVL)toxicology Reports]
*[http://www.niehs.nih.gov/ National Institute of Environmental Health Sciences]
*[http://cebs.niehs.nih.gov/cebs-browser/searchStudies.do?behavior=loadBlank Chemical effects in biological systems]
*[http://toxnet.nlm.nih.gov/ Toxnet]
*[http://potency.berkeley.edu/ The Carcinogenic Potency Database]
*[http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm National Toxicology program database]
*[http://www.epa.gov/ncct/dsstox/ DssTox public database network]
*[http://ecb.jrc.ec.europa.eu/esis/ European chemical substances information system]
*[http://www.ecetoc.org/ European centre for Ecotoxicology and Toxicology of chemicals]
*[http://www.atsdr.cdc.gov/toxfaq.html Agency for Toxic Substances & Disease Registry]
*[http://ctd.mdibl.org/ Comparative Toxicogenomics database]

==Sample Report==

{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FCD5B4"|'''S.No'''
|align = "center" bgcolor = "#FCD5B4"|'''Database'''
|align = "center" bgcolor = "#FCD5B4"|'''Compound/Substance Name'''
|align = "center" bgcolor = "#FCD5B4"|'''Information Available'''
|-
|align = "center" bgcolor = "#FCD5B4"|'''1'''
|align = "center"|[http://toxnet.nlm.nih.gov/ Toxicology Data Network]
|align = "center"|Paracetamol
|align = "center"|Chemical, Toxicological, and Environmental Health Data
|-
|align = "center" bgcolor = "#FCD5B4"|'''2'''
|align = "center"|[http://potency.berkeley.edu/ The Carcinogenic Potency Database]
|align = "center"|Dimethadione
|align = "center"|Rats and Mice: Cancer Test Summary ,Criteria for inclusion of experiments ,Standardization of average daily dose levels ,TD50 estimation for a standard lifespan etc.,
|-
|align = "center" bgcolor = "#FCD5B4"|'''3'''
|align = "center"|[http://ecb.jrc.ec.europa.eu/esis/ European chemical substances information system]
|align = "center"|Ibuprofen
|align = "center"|General Information,Biocidal Products Directive (Directive 98/8/EC) Information,Classification and Labelling Information,Export and Import of Dangerous Chemicals (Regulation (EC) No 689/2008) Information,HPV-LPV (High and Low Production Volume) Information,IUCLID & OECD Chemical Data Sheets and Export Files Information etc.,
|-
|}

Main Page

2009-11-18T15:57:29Z

Tony.kurian@dolcera.com: /* Business and Information Research Services */

__NOTOC__
===1. [[#Intellectual Property (IP) Services|Intellectual Property(IP) Services]]===
===2. [[#Business and Information Research Services|Business and Information Research Services]]===
===3. [[#Dolcera Technology Platform|Dolcera Technology Platform]]===

== Intellectual Property (IP) Services ==
{| style="border:1px solid #AAA; background:#E9E9E9;width:100%" align="center"
|-
! style="background:lightgrey;width:50%" valign = "top" |
===Life Sciences and Chemistry===
! style="background:lightgrey;width:50%" valign = "top" |
===Technology===
|-
| valign = "top" |
=== Landscape reports ===
* [[Alopecia - Hair Loss]] | ([http://www.youtube.com/watch?v=jAIoyKuKQ6o Video])
* [[Inflammation and cardiovascular drugs]]
* [[Hormone Sensitive Lipase]]
* [[RNA Interference]]
* [[RNAi Database sample wiki]]
* [[Choline Bitartarate]]
* [[Non-wovens]]
* [[Pressure sensitive adhesives]] | ([http://www.youtube.com/watch?v=plP3TzjYsiQ Video])
* [[Ureteral Stent]]
* [[Smart miniature drug delivery systems]]
* [[Silicone Hydrogel contact lens]]
* [[Biofuels database sample wiki]]
* [[SC Johnson]]
| valign = "top" |

=== Landscape Reports ===
* [[Hybrid Electric Vehicle Battery System]]
* [[Supply Chain RFID Applications]]
* [[Insurance sector]]
* [[CDMA Basics]]
* [[Quality of Service on CDMA platforms]]
* [[OLED - Organic Light Emitting Diode]]
* [[Carbon Nanotubes (CNT)]]
* [[Metallic and Ceramic construction materials]]
* [[Transactional memory]]
* [[Invalidation Search on a patent in the semiconductors space]]
* [[Golf Club Head Landscape]]

|-
| valign = "top" |

===STN Search Reports===
* [[Markush Search Report]]

=== Dashboard ===
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard - live]
** ([[Alopecia Areata Dashboard Screenshots|Screenshots only]])
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]
* [http://www.dolcera.com/website/demos/dna/main.html Sequence dashboard]
* [[Legal Updates Demo|Legal updates dashboard]]
* [http://client.dolcera.com/dashboard/dashboard.html?workfile_id=587 RNAi Dashboard]
| valign = "top" |

=== Dashboard ===
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=27 Automotive dashboard - live]
** [[Automotive Dashboard Screenshots|Screenshots only]]
* [http://client.dolcera.com/dashboard/dashboard.html?workfile_id=54 WiMAX dashboard - live]
** [[WiMAX Dashboard Screenshots|Screenshots only]]
* [http://www.dolcera.com/ipmapdemo/rfid_model.swf RFID dashboard]
|-
| valign = "top" |

=== Prior Art / Invalidation / FTO Search ===
* [http://dolcera.com/client/d8r3/hairloss_map.htm Alopecia/Hair loss IPMap]
* [[Markush Structure Search Sample]]
* [[Interferon For Treatment of Melanoma]]
==== Study: In re Bilski Impact ====
* [[In re Bilski Impact assessed from US PAIR Information]]
| valign = "top" |

=== Prior Art / Invalidation / FTO Search ===
* [[Prior Art Search Process]]
* [http://www.dolcera.com/ipmapdemo/satellite_antenna/ipmap.html Satellite Antenna IPMap]
* [http://www.dolcera.com/ipmapdemo/rfid/ipmap.html RFID IPMap]
* [http://www.dolcera.com/ipmapdemo/multimodal_apps/ipmap.html Multimodal Applications IPMap]
* [http://www.dolcera.com/ipmapdemo/Invalidation_US4825448.htm Invalidation Claim Map Sample]
|-
|}

===Clinical Trial Database===
*[[Clinical Trial Database]]

== Business and Information Research Services ==
{| style="border:1px solid #AAA; background:#E9E9E9;width:100%" align="center"
|-
! style="background:lightgrey" valign=top width=50%|
===Life Sciences and Chemistry===
! style="background:lightgrey" valign=top width=50%|
===Technology===
|-
| valign=top |
* [[Diabetes products and services]]
* [[Drug Metabolism]]
* [[Toxicology]]
* [[Osteoporosis]]
* [[Oral Diabetes Drugs]]
* [[Ureteral Stent]]
* [[Premium Coffee Consumers Market Segmentation|Premium Coffee - Market Positioning]]
* [[Dolcera's Poster on Industrial Biotechnology|Industrial biotechnology]]
* [[OTC products for acne treatment]]
* [[Botox - from Medical Procedure to Household Word]]
| valign=top |
* [[4G wireless technology developments]]
* [[HDTV in the US]]
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics Innovation Explorer]
* [[Web video]]
* [[OLED Mobile Phones Market Research and Analysis Report]] | ([http://www.viddler.com/explore/dolcera/videos/6/ Video])
* [[Virtualization]]
* [[Cloud Computing]]
* [[Estimation of liquid carrying vehicles in USA]]
* [[A market study on Hybrid vehicles and the concept of V2G]]
|-
! style="background:lightgrey" valign=top colspan=2 |

===Finance===
|-
| valign=top colspan=2 |
* [[Innovative personal finance products]]
* [[Life Insurance Industry in US]]
|}

== Dolcera Technology Platform ==
{| style="border:1px solid #AAA; background:#E9E9E9;width:100%" align="center"
|-
| align = "top" |
==== IP and Products dashboard ====
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard]
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]
* [[Legal Updates Demo|Legal updates dashboard]]
* [http://client.dolcera.com/dashboard/dashboard.html?workfile_id=54 4G wireless product and patent dashboard]

==== Patent-pathway mapping ====
* [[Inflammation and cardiovascular drugs#Interactive signaling pathways and patents|Patent-pathway mapping]]
==== Sequence dashboard ====
* [http://www.dolcera.com/website/demos/dna/main.html Sequence dashboard]

==== Design analysis ====
* [http://www.dolcera.com/website/demos/dental/main.html Dental Implant Design Analysis]

==== Innovation explorer ====
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics innovation explorer]
==== KPort ====
* [http://dolcera.com/website/demos/kport/main.html Collaboration Portal]

|-
|}

=== Dolcera Offerings summary ===
* [[Dolcera Offerings|Dolcera offerings summary]]

=== [[Technology Support]] ===

==Like any of these sample reports?==
 '''These are sample reports with brief analysis''' 
'''Dolcera can provide a comprehensive report customized to your needs'''
{|border="2" cellspacing="0" cellpadding="4" align="center" "
|style="background:lightgrey" align = "center" colspan = "3"|'''[mailto:info@dolcera.com Buy the customized report from Dolcera]'''
|-
| align = "center"| [http://www.dolcera.com/website_prod/services/ip-patent-analytics-services Patent Analytics Services]
|align = "center"| [http://www.dolcera.com/website_prod/services/business-research-services Market Research Services]
|align = "center"| [http://www.dolcera.com/website_prod/tools/patent-dashboard Purchase Patent Dashboard]
|-
|align = "center"| [http://www.dolcera.com/website_prod/services/ip-patent-analytics-services/patent-search/patent-landscapes Patent Landscape Services]
|align = "center"| [http://www.dolcera.com/website_prod/research-processes Dolcera Processes]
|align = "center"| [http://www.dolcera.com/website_prod/industries Industry Focus]
|-
|align = "center"| [http://www.dolcera.com/website_prod/services/ip-patent-analytics-services/patent-search/patent-landscapes Patent Search Services]
|align = "center"| [http://www.dolcera.com/website_prod/services/ip-patent-analytics-services/alerts-and-updates Patent Alerting Services]
|align = "center"| [http://www.dolcera.com/website_prod/tools Dolcera Tools]
|-
|}
 

----
{| style="border:1px solid #AAA; background:#E9E9E9" align="center"
|-
! style="background:lightgrey" | Contact Dolcera
|-
! style="background:lightgrey" | Samir Raiyani
|-
| '''Email''': [mailto:info@dolcera.com info@dolcera.com]
|-
| '''Phone''': +1-650-269-7952, +91-40-2355-3493
|}

File:Drug metabolism1.jpg

2009-11-18T12:09:10Z

Tony.kurian@dolcera.com:

Drug Metabolism

2009-11-18T12:08:44Z

Tony.kurian@dolcera.com:

[[Image:Drug metabolism1.jpg|right|370 px|Drug metabolism]]
==Introduction==
Drug metabolism is a detoxification function the human body possesses to defend itself from environment hostility.
Ideally, a drug should reach the site of action intact, cure the disease, and leave the body after it completes its mission.
However, drug developers often face the dilemma that a potential drug is either metabolized/excreted from the body too fast, that the drug can not reach its therapeutic effect, or too slow, that it stays in the body for a long time, causing side effects.(Drug is a xenobiotic that the normal human body doesn't need.) The study of drug metabolism, therefore, serves primarily two purposes
*To elucidate the function and fate of the drug
*To manipulate the metabolic process of a potential drug.

==Metabolism Sites==
The liver is the primary site for metabolism. It contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways:
*'''Phase I (functionalization reactions)'''. The enzymes involved in Phase I reactions are primarily located in the endoplasmic reticulum of the liver cell, they are called microsomal enzymes Eg. Oxidation and hydrolysis. The Phase I reaction introduces a functional group such as a hydroxyl group onto the molecule, or exposes a preexisting functional group
*'''Phase II (conjugation/biosynthetic reactions)''' This involves the introduction of a hydrophilic endogenous species, such as glucuronic acid or sulfate, to the drug molecule. Enzymes involved in phase II reactions are mainly located in the cytosol, except glucuronidation enzyme, which is also a microsomal enzyme.Phase II metabolism Drugs are usually lipophilic substances (Oil-like) so they can pass plasma membranes and reach the site of action. Phase II reaction connects this functional group to the endogenous species such as a glucuronic acid. The modified drug molecule may then be hydrophilic enough to be excreted
*'''Phase III reactions''' involves further biotransformation of conjugates.
Drug metabolism is basically a process that introduces hydrophilic functionailities onto the drug molecule to facilitate excretion.
When the drug molecule is oxidized, hydrolyzed, or covalently attached to a hydrophilic species, the whole molecule becomes more hydrophilic, and is excreted more easily.
Although liver is the primary site for metabolism, virtually all tissue cells have some metabolic activities. Other organs having significant metabolic activities include the gastrointestinal tract, kidneys, and lungs. When a drug is administrated orally, it undergoes metabolism in the GI track and the liver before reaching systemic circulation. This process is called first-pass metabolism. First-pass metabolism limits the oral bioavailability of drugs, sometimes significantly.

==Fate of Metabolized drugs==

*Drugs are ultimately excreted from the body through various routes.The kidney is the major organ for drug excretion. It excretes hydrophilic drug and drug metabolites through glomerular filtration.Macromolecules such as proteins are retained. Lipophilic drug molecules are not directly excreted from the kidney.Only after they are metabolized into more hydrophilic molecules, can they be excreted through the kidneys into the urine.
*Drugs and their metabolites are also excreted into bile. This is usually mediated by protein transporters. Drugs and their metabolites in bile are eventually released into the intestinal tract. The drugs may be reabsorbed into the body from the intestine. Drug metabolites such as glucuronide conjugates, may be converted back to the parent drug in the intestine through glucuronidase enzyme, and then reabsorbed into systemic circulation. This drug recycling process is called '''enterohepatic recycling'''.This process, if extensive, may prolong the half-life of the drug.
*The bile drugs and drug metabolites, if not reabsorbed by intestine, are excreted from the body through feces. Also, a variety of orally administrated drugs are excreted through feces because they are not absorbed through the intestine. Oral bioavailability constitutes a major challenge for drug developers. Other routes of excretion, such as sweat, tears, and saliva, are quantitatively less important. Excretion through breast milk is not important to the mother, but may be of key importance to the baby, because the drug may be toxic to the baby. Pulmonary excretion is important for anesthetic gases and vapor drugs.

==Metabolic changes - Mass Shifts==
List of mass shifts caused by metabolism of common functional groups.
*Glucuronidation: plus 176 u.
*Sulfation: plus 80 u.
*Oxidation (N-, S-): plus 16 u.
*Hydroxylation (aliphatic, aromatic): plus 16 u (or 32, if two sites).
*Dealkylation: minus the alkyl group: minus 14 u for a methyl group, and 28 u for an ethyl group.
*Hydrolysis: minus R-1 for ester hydrolysis into the acid.[http://ionsource.com/tutorial/metabolism/met_slide2.htm Source]

==Key Parameters==

*Maximum drug concentration (Cmax)
*Time to peak concentration Tmax (h)
*Absorption half-life t1/2(a) (h)
*Distribution half-life t1/2 (h)
*Elimination half-life t1/2(ß) (h)
*Area under curve (AUC) µg/ml/h
*Volume of distribution (Vd) mg/litre
*Absorption rate constant Ka (h)
*Distribution rate constant K (h)
*Elimination rate constant Ke (h)
*Mean residual time MRT (h)
*Therapeutic concentration tcp(ther)
*Body clearance CL (h)
[http://www.banglajol.info/index.php/BJVM/article/view/1344/1332 Source]

==Databases==
*[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
*[http://old.iupac.org/publications/epub/index.html#db IUPAC]
*[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
*[http://searchworks.stanford.edu/view/8232817 MDL Metabolite]
*[http://accelrys.com/products/accord/chemical-databases/metabolism.html Accelrys Metabolism Database]
*[http://www.druginteractioninfo.org/ Metabolism and Transport Drug interaction database]
*[http://www.fqs.pl/ Biofrontier/P450]
*[http://www.lhasalimited.org/ METEOR]
*[http://www.multicase.com/products/prod05.htm META]
*[http://www.compudrug.com/ MetabolExpert]
[http://books.google.co.in/books?id=eYJXj59Cg_UC&pg=PT51&lpg=PT51&dq=preclinical+drug+metabolism+database&source=bl&ots=75HigyNNky&sig=VDNW182OYEleEr0iLQKgtOrww4I&hl=en&ei=yAEAS4P7KIyGkQWl9fiDDA&sa=X&oi=book_result&ct=result&resnum=3&ved=0CBsQ6AEwAg#v=onepage&q=preclinical%20drug%20metabolism%20database&f=false Source]

==Sample Report==

{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FCD5B4"|'''S.No.'''
|align = "center" bgcolor = "#FCD5B4"|'''Database'''
|align = "center" bgcolor = "#FCD5B4"|'''Search by'''
|align = "center" bgcolor = "#FCD5B4"|'''Phase'''
|align = "center" bgcolor = "#FCD5B4"|'''Type of reaction'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Product'''
|-
|align = "center" bgcolor = "#FCD5B4"|'''1'''
|align = "center" rowspan = "3"|[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
|align = "center"|Reaction Type
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|Oxidation
|align = "center"|Carbon Oxidation
|align = "center"|Aromatics
|align = "center"|Diclofenac to 3<nowiki>’</nowiki>-hydroxy diclofenac
|-
|align = "center" bgcolor = "#FCD5B4"|'''2'''
|align = "center"|Functional Group - Alcohol
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Ethanol to Acetaldehyde
|-
|align = "center" bgcolor = "#FCD5B4"|'''3'''
|align = "center"|Substrate - Phenytoin
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Phenytoin to (S)-hydroxy-phenytoin
|-
|align = "center" bgcolor = "#FCD5B4"|'''4'''
|align = "center" rowspan = "2"|[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
|align = "center" rowspan = "2"|Pathway- Benzonitrile
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_map.html Click here for Pathway]
|-
|align = "center" bgcolor = "#FCD5B4"|'''5'''
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_image_map.html Click here for Pathway (Graphic 5K format)]
|-
|}

Drug Metabolism

2009-11-18T08:23:07Z

Tony.kurian@dolcera.com:

[[Image:Drug metabolism.jpg|right|350 px|Drug metabolism]]
==Introduction==
Drug metabolism is a detoxification function the human body possesses to defend itself from environment hostility.
Ideally, a drug should reach the site of action intact, cure the disease, and leave the body after it completes its mission.
However, drug developers often face the dilemma that a potential drug is either metabolized/excreted from the body too fast, that the drug can not reach its therapeutic effect, or too slow, that it stays in the body for a long time, causing side effects.(Drug is a xenobiotic that the normal human body doesn't need.) The study of drug metabolism, therefore, serves primarily two purposes
*To elucidate the function and fate of the drug
*To manipulate the metabolic process of a potential drug.

==Metabolism Sites==
The liver is the primary site for metabolism. It contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways:
*'''Phase I (functionalization reactions)'''. The enzymes involved in Phase I reactions are primarily located in the endoplasmic reticulum of the liver cell, they are called microsomal enzymes Eg. Oxidation and hydrolysis. The Phase I reaction introduces a functional group such as a hydroxyl group onto the molecule, or exposes a preexisting functional group
*'''Phase II (conjugation/biosynthetic reactions)''' This involves the introduction of a hydrophilic endogenous species, such as glucuronic acid or sulfate, to the drug molecule. Enzymes involved in phase II reactions are mainly located in the cytosol, except glucuronidation enzyme, which is also a microsomal enzyme.Phase II metabolism Drugs are usually lipophilic substances (Oil-like) so they can pass plasma membranes and reach the site of action. Phase II reaction connects this functional group to the endogenous species such as a glucuronic acid. The modified drug molecule may then be hydrophilic enough to be excreted
*'''Phase III reactions''' involves further biotransformation of conjugates.
Drug metabolism is basically a process that introduces hydrophilic functionailities onto the drug molecule to facilitate excretion.
When the drug molecule is oxidized, hydrolyzed, or covalently attached to a hydrophilic species, the whole molecule becomes more hydrophilic, and is excreted more easily.
Although liver is the primary site for metabolism, virtually all tissue cells have some metabolic activities. Other organs having significant metabolic activities include the gastrointestinal tract, kidneys, and lungs. When a drug is administrated orally, it undergoes metabolism in the GI track and the liver before reaching systemic circulation. This process is called first-pass metabolism. First-pass metabolism limits the oral bioavailability of drugs, sometimes significantly.

==Fate of Metabolized drugs==

*Drugs are ultimately excreted from the body through various routes.The kidney is the major organ for drug excretion. It excretes hydrophilic drug and drug metabolites through glomerular filtration.Macromolecules such as proteins are retained. Lipophilic drug molecules are not directly excreted from the kidney.Only after they are metabolized into more hydrophilic molecules, can they be excreted through the kidneys into the urine.
*Drugs and their metabolites are also excreted into bile. This is usually mediated by protein transporters. Drugs and their metabolites in bile are eventually released into the intestinal tract. The drugs may be reabsorbed into the body from the intestine. Drug metabolites such as glucuronide conjugates, may be converted back to the parent drug in the intestine through glucuronidase enzyme, and then reabsorbed into systemic circulation. This drug recycling process is called '''enterohepatic recycling'''.This process, if extensive, may prolong the half-life of the drug.
*The bile drugs and drug metabolites, if not reabsorbed by intestine, are excreted from the body through feces. Also, a variety of orally administrated drugs are excreted through feces because they are not absorbed through the intestine. Oral bioavailability constitutes a major challenge for drug developers. Other routes of excretion, such as sweat, tears, and saliva, are quantitatively less important. Excretion through breast milk is not important to the mother, but may be of key importance to the baby, because the drug may be toxic to the baby. Pulmonary excretion is important for anesthetic gases and vapor drugs.

==Metabolic changes - Mass Shifts==
List of mass shifts caused by metabolism of common functional groups.
*Glucuronidation: plus 176 u.
*Sulfation: plus 80 u.
*Oxidation (N-, S-): plus 16 u.
*Hydroxylation (aliphatic, aromatic): plus 16 u (or 32, if two sites).
*Dealkylation: minus the alkyl group: minus 14 u for a methyl group, and 28 u for an ethyl group.
*Hydrolysis: minus R-1 for ester hydrolysis into the acid.[http://ionsource.com/tutorial/metabolism/met_slide2.htm Source]

==Key Parameters==

*Maximum drug concentration (Cmax)
*Time to peak concentration Tmax (h)
*Absorption half-life t1/2(a) (h)
*Distribution half-life t1/2 (h)
*Elimination half-life t1/2(ß) (h)
*Area under curve (AUC) µg/ml/h
*Volume of distribution (Vd) mg/litre
*Absorption rate constant Ka (h)
*Distribution rate constant K (h)
*Elimination rate constant Ke (h)
*Mean residual time MRT (h)
*Therapeutic concentration tcp(ther)
*Body clearance CL (h)
[http://www.banglajol.info/index.php/BJVM/article/view/1344/1332 Source]

==Databases==
*[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
*[http://old.iupac.org/publications/epub/index.html#db IUPAC]
*[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
*[http://searchworks.stanford.edu/view/8232817 MDL Metabolite]
*[http://accelrys.com/products/accord/chemical-databases/metabolism.html Accelrys Metabolism Database]
*[http://www.druginteractioninfo.org/ Metabolism and Transport Drug interaction database]
*[http://www.fqs.pl/ Biofrontier/P450]
*[http://www.lhasalimited.org/ METEOR]
*[http://www.multicase.com/products/prod05.htm META]
*[http://www.compudrug.com/ MetabolExpert]
[http://books.google.co.in/books?id=eYJXj59Cg_UC&pg=PT51&lpg=PT51&dq=preclinical+drug+metabolism+database&source=bl&ots=75HigyNNky&sig=VDNW182OYEleEr0iLQKgtOrww4I&hl=en&ei=yAEAS4P7KIyGkQWl9fiDDA&sa=X&oi=book_result&ct=result&resnum=3&ved=0CBsQ6AEwAg#v=onepage&q=preclinical%20drug%20metabolism%20database&f=false Source]

==Sample Report==

{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FCD5B4"|'''S.No.'''
|align = "center" bgcolor = "#FCD5B4"|'''Database'''
|align = "center" bgcolor = "#FCD5B4"|'''Search by'''
|align = "center" bgcolor = "#FCD5B4"|'''Phase'''
|align = "center" bgcolor = "#FCD5B4"|'''Type of reaction'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Product'''
|-
|align = "center" bgcolor = "#FCD5B4"|'''1'''
|align = "center" rowspan = "3"|[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
|align = "center"|Reaction Type
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|Oxidation
|align = "center"|Carbon Oxidation
|align = "center"|Aromatics
|align = "center"|Diclofenac to 3<nowiki>’</nowiki>-hydroxy diclofenac
|-
|align = "center" bgcolor = "#FCD5B4"|'''2'''
|align = "center"|Functional Group - Alcohol
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Ethanol to Acetaldehyde
|-
|align = "center" bgcolor = "#FCD5B4"|'''3'''
|align = "center"|Substrate - Phenytoin
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Phenytoin to (S)-hydroxy-phenytoin
|-
|align = "center" bgcolor = "#FCD5B4"|'''4'''
|align = "center" rowspan = "2"|[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
|align = "center" rowspan = "2"|Pathway- Benzonitrile
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_map.html Click here for Pathway]
|-
|align = "center" bgcolor = "#FCD5B4"|'''5'''
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_image_map.html Click here for Pathway (Graphic 5K format)]
|-
|}

Drug Metabolism

2009-11-18T08:22:49Z

Tony.kurian@dolcera.com:

[[Image:Drug metabolism.jpg|right|310 px|Drug metabolism]]
==Introduction==
Drug metabolism is a detoxification function the human body possesses to defend itself from environment hostility.
Ideally, a drug should reach the site of action intact, cure the disease, and leave the body after it completes its mission.
However, drug developers often face the dilemma that a potential drug is either metabolized/excreted from the body too fast, that the drug can not reach its therapeutic effect, or too slow, that it stays in the body for a long time, causing side effects.(Drug is a xenobiotic that the normal human body doesn't need.) The study of drug metabolism, therefore, serves primarily two purposes
*To elucidate the function and fate of the drug
*To manipulate the metabolic process of a potential drug.

==Metabolism Sites==
The liver is the primary site for metabolism. It contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways:
*'''Phase I (functionalization reactions)'''. The enzymes involved in Phase I reactions are primarily located in the endoplasmic reticulum of the liver cell, they are called microsomal enzymes Eg. Oxidation and hydrolysis. The Phase I reaction introduces a functional group such as a hydroxyl group onto the molecule, or exposes a preexisting functional group
*'''Phase II (conjugation/biosynthetic reactions)''' This involves the introduction of a hydrophilic endogenous species, such as glucuronic acid or sulfate, to the drug molecule. Enzymes involved in phase II reactions are mainly located in the cytosol, except glucuronidation enzyme, which is also a microsomal enzyme.Phase II metabolism Drugs are usually lipophilic substances (Oil-like) so they can pass plasma membranes and reach the site of action. Phase II reaction connects this functional group to the endogenous species such as a glucuronic acid. The modified drug molecule may then be hydrophilic enough to be excreted
*'''Phase III reactions''' involves further biotransformation of conjugates.
Drug metabolism is basically a process that introduces hydrophilic functionailities onto the drug molecule to facilitate excretion.
When the drug molecule is oxidized, hydrolyzed, or covalently attached to a hydrophilic species, the whole molecule becomes more hydrophilic, and is excreted more easily.
Although liver is the primary site for metabolism, virtually all tissue cells have some metabolic activities. Other organs having significant metabolic activities include the gastrointestinal tract, kidneys, and lungs. When a drug is administrated orally, it undergoes metabolism in the GI track and the liver before reaching systemic circulation. This process is called first-pass metabolism. First-pass metabolism limits the oral bioavailability of drugs, sometimes significantly.

==Fate of Metabolized drugs==

*Drugs are ultimately excreted from the body through various routes.The kidney is the major organ for drug excretion. It excretes hydrophilic drug and drug metabolites through glomerular filtration.Macromolecules such as proteins are retained. Lipophilic drug molecules are not directly excreted from the kidney.Only after they are metabolized into more hydrophilic molecules, can they be excreted through the kidneys into the urine.
*Drugs and their metabolites are also excreted into bile. This is usually mediated by protein transporters. Drugs and their metabolites in bile are eventually released into the intestinal tract. The drugs may be reabsorbed into the body from the intestine. Drug metabolites such as glucuronide conjugates, may be converted back to the parent drug in the intestine through glucuronidase enzyme, and then reabsorbed into systemic circulation. This drug recycling process is called '''enterohepatic recycling'''.This process, if extensive, may prolong the half-life of the drug.
*The bile drugs and drug metabolites, if not reabsorbed by intestine, are excreted from the body through feces. Also, a variety of orally administrated drugs are excreted through feces because they are not absorbed through the intestine. Oral bioavailability constitutes a major challenge for drug developers. Other routes of excretion, such as sweat, tears, and saliva, are quantitatively less important. Excretion through breast milk is not important to the mother, but may be of key importance to the baby, because the drug may be toxic to the baby. Pulmonary excretion is important for anesthetic gases and vapor drugs.

==Metabolic changes - Mass Shifts==
List of mass shifts caused by metabolism of common functional groups.
*Glucuronidation: plus 176 u.
*Sulfation: plus 80 u.
*Oxidation (N-, S-): plus 16 u.
*Hydroxylation (aliphatic, aromatic): plus 16 u (or 32, if two sites).
*Dealkylation: minus the alkyl group: minus 14 u for a methyl group, and 28 u for an ethyl group.
*Hydrolysis: minus R-1 for ester hydrolysis into the acid.[http://ionsource.com/tutorial/metabolism/met_slide2.htm Source]

==Key Parameters==

*Maximum drug concentration (Cmax)
*Time to peak concentration Tmax (h)
*Absorption half-life t1/2(a) (h)
*Distribution half-life t1/2 (h)
*Elimination half-life t1/2(ß) (h)
*Area under curve (AUC) µg/ml/h
*Volume of distribution (Vd) mg/litre
*Absorption rate constant Ka (h)
*Distribution rate constant K (h)
*Elimination rate constant Ke (h)
*Mean residual time MRT (h)
*Therapeutic concentration tcp(ther)
*Body clearance CL (h)
[http://www.banglajol.info/index.php/BJVM/article/view/1344/1332 Source]

==Databases==
*[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
*[http://old.iupac.org/publications/epub/index.html#db IUPAC]
*[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
*[http://searchworks.stanford.edu/view/8232817 MDL Metabolite]
*[http://accelrys.com/products/accord/chemical-databases/metabolism.html Accelrys Metabolism Database]
*[http://www.druginteractioninfo.org/ Metabolism and Transport Drug interaction database]
*[http://www.fqs.pl/ Biofrontier/P450]
*[http://www.lhasalimited.org/ METEOR]
*[http://www.multicase.com/products/prod05.htm META]
*[http://www.compudrug.com/ MetabolExpert]
[http://books.google.co.in/books?id=eYJXj59Cg_UC&pg=PT51&lpg=PT51&dq=preclinical+drug+metabolism+database&source=bl&ots=75HigyNNky&sig=VDNW182OYEleEr0iLQKgtOrww4I&hl=en&ei=yAEAS4P7KIyGkQWl9fiDDA&sa=X&oi=book_result&ct=result&resnum=3&ved=0CBsQ6AEwAg#v=onepage&q=preclinical%20drug%20metabolism%20database&f=false Source]

==Sample Report==

{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FCD5B4"|'''S.No.'''
|align = "center" bgcolor = "#FCD5B4"|'''Database'''
|align = "center" bgcolor = "#FCD5B4"|'''Search by'''
|align = "center" bgcolor = "#FCD5B4"|'''Phase'''
|align = "center" bgcolor = "#FCD5B4"|'''Type of reaction'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Product'''
|-
|align = "center" bgcolor = "#FCD5B4"|'''1'''
|align = "center" rowspan = "3"|[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
|align = "center"|Reaction Type
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|Oxidation
|align = "center"|Carbon Oxidation
|align = "center"|Aromatics
|align = "center"|Diclofenac to 3<nowiki>’</nowiki>-hydroxy diclofenac
|-
|align = "center" bgcolor = "#FCD5B4"|'''2'''
|align = "center"|Functional Group - Alcohol
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Ethanol to Acetaldehyde
|-
|align = "center" bgcolor = "#FCD5B4"|'''3'''
|align = "center"|Substrate - Phenytoin
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Phenytoin to (S)-hydroxy-phenytoin
|-
|align = "center" bgcolor = "#FCD5B4"|'''4'''
|align = "center" rowspan = "2"|[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
|align = "center" rowspan = "2"|Pathway- Benzonitrile
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_map.html Click here for Pathway]
|-
|align = "center" bgcolor = "#FCD5B4"|'''5'''
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_image_map.html Click here for Pathway (Graphic 5K format)]
|-
|}

Drug Metabolism

2009-11-18T08:22:22Z

Tony.kurian@dolcera.com:

[[Image:Drug metabolism.jpg|thumb|right|310 px|Drug metabolism]]
==Introduction==
Drug metabolism is a detoxification function the human body possesses to defend itself from environment hostility.
Ideally, a drug should reach the site of action intact, cure the disease, and leave the body after it completes its mission.
However, drug developers often face the dilemma that a potential drug is either metabolized/excreted from the body too fast, that the drug can not reach its therapeutic effect, or too slow, that it stays in the body for a long time, causing side effects.(Drug is a xenobiotic that the normal human body doesn't need.) The study of drug metabolism, therefore, serves primarily two purposes
*To elucidate the function and fate of the drug
*To manipulate the metabolic process of a potential drug.

==Metabolism Sites==
The liver is the primary site for metabolism. It contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways:
*'''Phase I (functionalization reactions)'''. The enzymes involved in Phase I reactions are primarily located in the endoplasmic reticulum of the liver cell, they are called microsomal enzymes Eg. Oxidation and hydrolysis. The Phase I reaction introduces a functional group such as a hydroxyl group onto the molecule, or exposes a preexisting functional group
*'''Phase II (conjugation/biosynthetic reactions)''' This involves the introduction of a hydrophilic endogenous species, such as glucuronic acid or sulfate, to the drug molecule. Enzymes involved in phase II reactions are mainly located in the cytosol, except glucuronidation enzyme, which is also a microsomal enzyme.Phase II metabolism Drugs are usually lipophilic substances (Oil-like) so they can pass plasma membranes and reach the site of action. Phase II reaction connects this functional group to the endogenous species such as a glucuronic acid. The modified drug molecule may then be hydrophilic enough to be excreted
*'''Phase III reactions''' involves further biotransformation of conjugates.
Drug metabolism is basically a process that introduces hydrophilic functionailities onto the drug molecule to facilitate excretion.
When the drug molecule is oxidized, hydrolyzed, or covalently attached to a hydrophilic species, the whole molecule becomes more hydrophilic, and is excreted more easily.
Although liver is the primary site for metabolism, virtually all tissue cells have some metabolic activities. Other organs having significant metabolic activities include the gastrointestinal tract, kidneys, and lungs. When a drug is administrated orally, it undergoes metabolism in the GI track and the liver before reaching systemic circulation. This process is called first-pass metabolism. First-pass metabolism limits the oral bioavailability of drugs, sometimes significantly.

==Fate of Metabolized drugs==

*Drugs are ultimately excreted from the body through various routes.The kidney is the major organ for drug excretion. It excretes hydrophilic drug and drug metabolites through glomerular filtration.Macromolecules such as proteins are retained. Lipophilic drug molecules are not directly excreted from the kidney.Only after they are metabolized into more hydrophilic molecules, can they be excreted through the kidneys into the urine.
*Drugs and their metabolites are also excreted into bile. This is usually mediated by protein transporters. Drugs and their metabolites in bile are eventually released into the intestinal tract. The drugs may be reabsorbed into the body from the intestine. Drug metabolites such as glucuronide conjugates, may be converted back to the parent drug in the intestine through glucuronidase enzyme, and then reabsorbed into systemic circulation. This drug recycling process is called '''enterohepatic recycling'''.This process, if extensive, may prolong the half-life of the drug.
*The bile drugs and drug metabolites, if not reabsorbed by intestine, are excreted from the body through feces. Also, a variety of orally administrated drugs are excreted through feces because they are not absorbed through the intestine. Oral bioavailability constitutes a major challenge for drug developers. Other routes of excretion, such as sweat, tears, and saliva, are quantitatively less important. Excretion through breast milk is not important to the mother, but may be of key importance to the baby, because the drug may be toxic to the baby. Pulmonary excretion is important for anesthetic gases and vapor drugs.

==Metabolic changes - Mass Shifts==
List of mass shifts caused by metabolism of common functional groups.
*Glucuronidation: plus 176 u.
*Sulfation: plus 80 u.
*Oxidation (N-, S-): plus 16 u.
*Hydroxylation (aliphatic, aromatic): plus 16 u (or 32, if two sites).
*Dealkylation: minus the alkyl group: minus 14 u for a methyl group, and 28 u for an ethyl group.
*Hydrolysis: minus R-1 for ester hydrolysis into the acid.[http://ionsource.com/tutorial/metabolism/met_slide2.htm Source]

==Key Parameters==

*Maximum drug concentration (Cmax)
*Time to peak concentration Tmax (h)
*Absorption half-life t1/2(a) (h)
*Distribution half-life t1/2 (h)
*Elimination half-life t1/2(ß) (h)
*Area under curve (AUC) µg/ml/h
*Volume of distribution (Vd) mg/litre
*Absorption rate constant Ka (h)
*Distribution rate constant K (h)
*Elimination rate constant Ke (h)
*Mean residual time MRT (h)
*Therapeutic concentration tcp(ther)
*Body clearance CL (h)
[http://www.banglajol.info/index.php/BJVM/article/view/1344/1332 Source]

==Databases==
*[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
*[http://old.iupac.org/publications/epub/index.html#db IUPAC]
*[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
*[http://searchworks.stanford.edu/view/8232817 MDL Metabolite]
*[http://accelrys.com/products/accord/chemical-databases/metabolism.html Accelrys Metabolism Database]
*[http://www.druginteractioninfo.org/ Metabolism and Transport Drug interaction database]
*[http://www.fqs.pl/ Biofrontier/P450]
*[http://www.lhasalimited.org/ METEOR]
*[http://www.multicase.com/products/prod05.htm META]
*[http://www.compudrug.com/ MetabolExpert]
[http://books.google.co.in/books?id=eYJXj59Cg_UC&pg=PT51&lpg=PT51&dq=preclinical+drug+metabolism+database&source=bl&ots=75HigyNNky&sig=VDNW182OYEleEr0iLQKgtOrww4I&hl=en&ei=yAEAS4P7KIyGkQWl9fiDDA&sa=X&oi=book_result&ct=result&resnum=3&ved=0CBsQ6AEwAg#v=onepage&q=preclinical%20drug%20metabolism%20database&f=false Source]

==Sample Report==

{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FCD5B4"|'''S.No.'''
|align = "center" bgcolor = "#FCD5B4"|'''Database'''
|align = "center" bgcolor = "#FCD5B4"|'''Search by'''
|align = "center" bgcolor = "#FCD5B4"|'''Phase'''
|align = "center" bgcolor = "#FCD5B4"|'''Type of reaction'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Product'''
|-
|align = "center" bgcolor = "#FCD5B4"|'''1'''
|align = "center" rowspan = "3"|[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
|align = "center"|Reaction Type
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|Oxidation
|align = "center"|Carbon Oxidation
|align = "center"|Aromatics
|align = "center"|Diclofenac to 3<nowiki>’</nowiki>-hydroxy diclofenac
|-
|align = "center" bgcolor = "#FCD5B4"|'''2'''
|align = "center"|Functional Group - Alcohol
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Ethanol to Acetaldehyde
|-
|align = "center" bgcolor = "#FCD5B4"|'''3'''
|align = "center"|Substrate - Phenytoin
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Phenytoin to (S)-hydroxy-phenytoin
|-
|align = "center" bgcolor = "#FCD5B4"|'''4'''
|align = "center" rowspan = "2"|[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
|align = "center" rowspan = "2"|Pathway- Benzonitrile
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_map.html Click here for Pathway]
|-
|align = "center" bgcolor = "#FCD5B4"|'''5'''
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_image_map.html Click here for Pathway (Graphic 5K format)]
|-
|}

File:Drug metabolism.jpg

2009-11-18T08:19:42Z

Tony.kurian@dolcera.com:

Drug Metabolism

2009-11-18T08:19:00Z

Tony.kurian@dolcera.com:

[[Image:Drug metabolism.jpg|thumb|right|350 px|Drug metabolism]]
==Introduction==
Drug metabolism is a detoxification function the human body possesses to defend itself from environment hostility.
Ideally, a drug should reach the site of action intact, cure the disease, and leave the body after it completes its mission.
However, drug developers often face the dilemma that a potential drug is either metabolized/excreted from the body too fast, that the drug can not reach its therapeutic effect, or too slow, that it stays in the body for a long time, causing side effects.(Drug is a xenobiotic that the normal human body doesn't need.) The study of drug metabolism, therefore, serves primarily two purposes
*To elucidate the function and fate of the drug
*To manipulate the metabolic process of a potential drug.

==Metabolism Sites==
The liver is the primary site for metabolism. It contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways:
*'''Phase I (functionalization reactions)'''. The enzymes involved in Phase I reactions are primarily located in the endoplasmic reticulum of the liver cell, they are called microsomal enzymes Eg. Oxidation and hydrolysis. The Phase I reaction introduces a functional group such as a hydroxyl group onto the molecule, or exposes a preexisting functional group
*'''Phase II (conjugation/biosynthetic reactions)''' This involves the introduction of a hydrophilic endogenous species, such as glucuronic acid or sulfate, to the drug molecule. Enzymes involved in phase II reactions are mainly located in the cytosol, except glucuronidation enzyme, which is also a microsomal enzyme.Phase II metabolism Drugs are usually lipophilic substances (Oil-like) so they can pass plasma membranes and reach the site of action. Phase II reaction connects this functional group to the endogenous species such as a glucuronic acid. The modified drug molecule may then be hydrophilic enough to be excreted
*'''Phase III reactions''' involves further biotransformation of conjugates.
Drug metabolism is basically a process that introduces hydrophilic functionailities onto the drug molecule to facilitate excretion.
When the drug molecule is oxidized, hydrolyzed, or covalently attached to a hydrophilic species, the whole molecule becomes more hydrophilic, and is excreted more easily.
Although liver is the primary site for metabolism, virtually all tissue cells have some metabolic activities. Other organs having significant metabolic activities include the gastrointestinal tract, kidneys, and lungs. When a drug is administrated orally, it undergoes metabolism in the GI track and the liver before reaching systemic circulation. This process is called first-pass metabolism. First-pass metabolism limits the oral bioavailability of drugs, sometimes significantly.

==Fate of Metabolized drugs==

*Drugs are ultimately excreted from the body through various routes.The kidney is the major organ for drug excretion. It excretes hydrophilic drug and drug metabolites through glomerular filtration.Macromolecules such as proteins are retained. Lipophilic drug molecules are not directly excreted from the kidney.Only after they are metabolized into more hydrophilic molecules, can they be excreted through the kidneys into the urine.
*Drugs and their metabolites are also excreted into bile. This is usually mediated by protein transporters. Drugs and their metabolites in bile are eventually released into the intestinal tract. The drugs may be reabsorbed into the body from the intestine. Drug metabolites such as glucuronide conjugates, may be converted back to the parent drug in the intestine through glucuronidase enzyme, and then reabsorbed into systemic circulation. This drug recycling process is called '''enterohepatic recycling'''.This process, if extensive, may prolong the half-life of the drug.
*The bile drugs and drug metabolites, if not reabsorbed by intestine, are excreted from the body through feces. Also, a variety of orally administrated drugs are excreted through feces because they are not absorbed through the intestine. Oral bioavailability constitutes a major challenge for drug developers. Other routes of excretion, such as sweat, tears, and saliva, are quantitatively less important. Excretion through breast milk is not important to the mother, but may be of key importance to the baby, because the drug may be toxic to the baby. Pulmonary excretion is important for anesthetic gases and vapor drugs.

==Metabolic changes - Mass Shifts==
List of mass shifts caused by metabolism of common functional groups.
*Glucuronidation: plus 176 u.
*Sulfation: plus 80 u.
*Oxidation (N-, S-): plus 16 u.
*Hydroxylation (aliphatic, aromatic): plus 16 u (or 32, if two sites).
*Dealkylation: minus the alkyl group: minus 14 u for a methyl group, and 28 u for an ethyl group.
*Hydrolysis: minus R-1 for ester hydrolysis into the acid.[http://ionsource.com/tutorial/metabolism/met_slide2.htm Source]

==Key Parameters==

*Maximum drug concentration (Cmax)
*Time to peak concentration Tmax (h)
*Absorption half-life t1/2(a) (h)
*Distribution half-life t1/2 (h)
*Elimination half-life t1/2(ß) (h)
*Area under curve (AUC) µg/ml/h
*Volume of distribution (Vd) mg/litre
*Absorption rate constant Ka (h)
*Distribution rate constant K (h)
*Elimination rate constant Ke (h)
*Mean residual time MRT (h)
*Therapeutic concentration tcp(ther)
*Body clearance CL (h)
[http://www.banglajol.info/index.php/BJVM/article/view/1344/1332 Source]

==Databases==
*[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
*[http://old.iupac.org/publications/epub/index.html#db IUPAC]
*[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
*[http://searchworks.stanford.edu/view/8232817 MDL Metabolite]
*[http://accelrys.com/products/accord/chemical-databases/metabolism.html Accelrys Metabolism Database]
*[http://www.druginteractioninfo.org/ Metabolism and Transport Drug interaction database]
*[http://www.fqs.pl/ Biofrontier/P450]
*[http://www.lhasalimited.org/ METEOR]
*[http://www.multicase.com/products/prod05.htm META]
*[http://www.compudrug.com/ MetabolExpert]
[http://books.google.co.in/books?id=eYJXj59Cg_UC&pg=PT51&lpg=PT51&dq=preclinical+drug+metabolism+database&source=bl&ots=75HigyNNky&sig=VDNW182OYEleEr0iLQKgtOrww4I&hl=en&ei=yAEAS4P7KIyGkQWl9fiDDA&sa=X&oi=book_result&ct=result&resnum=3&ved=0CBsQ6AEwAg#v=onepage&q=preclinical%20drug%20metabolism%20database&f=false Source]

==Sample Report==

{|border="2" cellspacing="0" cellpadding="4" width="100%"
|align = "center" bgcolor = "#FCD5B4"|'''S.No.'''
|align = "center" bgcolor = "#FCD5B4"|'''Database'''
|align = "center" bgcolor = "#FCD5B4"|'''Search by'''
|align = "center" bgcolor = "#FCD5B4"|'''Phase'''
|align = "center" bgcolor = "#FCD5B4"|'''Type of reaction'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Sub sub Type'''
|align = "center" bgcolor = "#FCD5B4"|'''Product'''
|-
|align = "center" bgcolor = "#FCD5B4"|'''1'''
|align = "center" rowspan = "3"|[http://www.drugmetabolism.co.uk/ReactionSelector2.aspx Drug Metabolism]
|align = "center"|Reaction Type
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|Oxidation
|align = "center"|Carbon Oxidation
|align = "center"|Aromatics
|align = "center"|Diclofenac to 3<nowiki>’</nowiki>-hydroxy diclofenac
|-
|align = "center" bgcolor = "#FCD5B4"|'''2'''
|align = "center"|Functional Group - Alcohol
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Ethanol to Acetaldehyde
|-
|align = "center" bgcolor = "#FCD5B4"|'''3'''
|align = "center"|Substrate - Phenytoin
|align = "center"|Phase I(Functionalisation reactions)
|align = "center"|
|align = "center"|
|align = "center"|
|align = "center"|Phenytoin to (S)-hydroxy-phenytoin
|-
|align = "center" bgcolor = "#FCD5B4"|'''4'''
|align = "center" rowspan = "2"|[http://umbbd.msi.umn.edu/ University of Minnesota Biocatalysis/Biodegradation database]
|align = "center" rowspan = "2"|Pathway- Benzonitrile
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_map.html Click here for Pathway]
|-
|align = "center" bgcolor = "#FCD5B4"|'''5'''
|
|
|
|
|align = "center"|[http://umbbd.msi.umn.edu/bzn/bzn_image_map.html Click here for Pathway (Graphic 5K format)]
|-
|}

Main Page

2009-11-18T08:17:55Z

Tony.kurian@dolcera.com: /* Business and Information Research Services */

__NOTOC__
===1. [[#Intellectual Property (IP) Services|Intellectual Property(IP) Services]]===
===2. [[#Business and Information Research Services|Business and Information Research Services]]===
===3. [[#Dolcera Technology Platform|Dolcera Technology Platform]]===

== Intellectual Property (IP) Services ==
{| style="border:1px solid #AAA; background:#E9E9E9;width:100%" align="center"
|-
! style="background:lightgrey;width:50%" valign = "top" |
===Life Sciences and Chemistry===
! style="background:lightgrey;width:50%" valign = "top" |
===Technology===
|-
| valign = "top" |
=== Landscape reports ===
* [[Alopecia - Hair Loss]] | ([http://www.youtube.com/watch?v=jAIoyKuKQ6o Video])
* [[Inflammation and cardiovascular drugs]]
* [[Hormone Sensitive Lipase]]
* [[RNA Interference]]
* [[RNAi Database sample wiki]]
* [[Choline Bitartarate]]
* [[Non-wovens]]
* [[Pressure sensitive adhesives]] | ([http://www.youtube.com/watch?v=plP3TzjYsiQ Video])
* [[Ureteral Stent]]
* [[Smart miniature drug delivery systems]]
* [[Silicone Hydrogel contact lens]]
* [[Biofuels database sample wiki]]
* [[SC Johnson]]
| valign = "top" |

=== Landscape Reports ===
* [[Hybrid Electric Vehicle Battery System]]
* [[Supply Chain RFID Applications]]
* [[Insurance sector]]
* [[CDMA Basics]]
* [[Quality of Service on CDMA platforms]]
* [[OLED - Organic Light Emitting Diode]]
* [[Carbon Nanotubes (CNT)]]
* [[Metallic and Ceramic construction materials]]
* [[Transactional memory]]
* [[Invalidation Search on a patent in the semiconductors space]]
* [[Golf Club Head Landscape]]

|-
| valign = "top" |

===STN Search Reports===
* [[Markush Search Report]]

=== Dashboard ===
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard - live]
** ([[Alopecia Areata Dashboard Screenshots|Screenshots only]])
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]
* [http://www.dolcera.com/website/demos/dna/main.html Sequence dashboard]
* [[Legal Updates Demo|Legal updates dashboard]]
* [http://client.dolcera.com/dashboard/dashboard.html?workfile_id=587 RNAi Dashboard]
| valign = "top" |

=== Dashboard ===
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=27 Automotive dashboard - live]
** [[Automotive Dashboard Screenshots|Screenshots only]]
* [http://client.dolcera.com/dashboard/dashboard.html?workfile_id=54 WiMAX dashboard - live]
** [[WiMAX Dashboard Screenshots|Screenshots only]]
* [http://www.dolcera.com/ipmapdemo/rfid_model.swf RFID dashboard]
|-
| valign = "top" |

=== Prior Art / Invalidation / FTO Search ===
* [http://dolcera.com/client/d8r3/hairloss_map.htm Alopecia/Hair loss IPMap]
* [[Markush Structure Search Sample]]
* [[Interferon For Treatment of Melanoma]]
==== Study: In re Bilski Impact ====
* [[In re Bilski Impact assessed from US PAIR Information]]
| valign = "top" |

=== Prior Art / Invalidation / FTO Search ===
* [[Prior Art Search Process]]
* [http://www.dolcera.com/ipmapdemo/satellite_antenna/ipmap.html Satellite Antenna IPMap]
* [http://www.dolcera.com/ipmapdemo/rfid/ipmap.html RFID IPMap]
* [http://www.dolcera.com/ipmapdemo/multimodal_apps/ipmap.html Multimodal Applications IPMap]
* [http://www.dolcera.com/ipmapdemo/Invalidation_US4825448.htm Invalidation Claim Map Sample]
|-
|}

===Clinical Trial Database===
*[[Clinical Trial Database]]

== Business and Information Research Services ==
{| style="border:1px solid #AAA; background:#E9E9E9;width:100%" align="center"
|-
! style="background:lightgrey" valign=top width=50%|
===Life Sciences and Chemistry===
! style="background:lightgrey" valign=top width=50%|
===Technology===
|-
| valign=top |
* [[Diabetes products and services]]
* [[Drug Metabolism]]
* [[Osteoporosis]]
* [[Oral Diabetes Drugs]]
* [[Ureteral Stent]]
* [[Premium Coffee Consumers Market Segmentation|Premium Coffee - Market Positioning]]
* [[Dolcera's Poster on Industrial Biotechnology|Industrial biotechnology]]
* [[OTC products for acne treatment]]
* [[Botox - from Medical Procedure to Household Word]]
| valign=top |
* [[4G wireless technology developments]]
* [[HDTV in the US]]
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics Innovation Explorer]
* [[Web video]]
* [[OLED Mobile Phones Market Research and Analysis Report]] | ([http://www.viddler.com/explore/dolcera/videos/6/ Video])
* [[Virtualization]]
* [[Cloud Computing]]
* [[Estimation of liquid carrying vehicles in USA]]
* [[A market study on Hybrid vehicles and the concept of V2G]]
|-
! style="background:lightgrey" valign=top colspan=2 |

===Finance===
|-
| valign=top colspan=2 |
* [[Innovative personal finance products]]
* [[Life Insurance Industry in US]]
|}

== Dolcera Technology Platform ==
{| style="border:1px solid #AAA; background:#E9E9E9;width:100%" align="center"
|-
| align = "top" |
==== IP and Products dashboard ====
* [http://client.dolcera.com/dashboard/dashboard.html?workfilegroup_id=10 Alopecia areata dashboard]
* [http://www.dolcera.com/ipmapdemo/stent_model.swf Stent dashboard]
* [[Legal Updates Demo|Legal updates dashboard]]
* [http://client.dolcera.com/dashboard/dashboard.html?workfile_id=54 4G wireless product and patent dashboard]

==== Patent-pathway mapping ====
* [[Inflammation and cardiovascular drugs#Interactive signaling pathways and patents|Patent-pathway mapping]]
==== Sequence dashboard ====
* [http://www.dolcera.com/website/demos/dna/main.html Sequence dashboard]

==== Design analysis ====
* [http://www.dolcera.com/website/demos/dental/main.html Dental Implant Design Analysis]

==== Innovation explorer ====
* [http://www.dolcera.com/ipmapdemo/innovation_explorer/innovation_explorer.html Household robotics innovation explorer]
==== KPort ====
* [http://dolcera.com/website/demos/kport/main.html Collaboration Portal]

|-
|}

=== Dolcera Offerings summary ===
* [[Dolcera Offerings|Dolcera offerings summary]]

=== [[Technology Support]] ===

==Like any of these sample reports?==
 '''These are sample reports with brief analysis''' 
'''Dolcera can provide a comprehensive report customized to your needs'''
{|border="2" cellspacing="0" cellpadding="4" align="center" "
|style="background:lightgrey" align = "center" colspan = "3"|'''[mailto:info@dolcera.com Buy the customized report from Dolcera]'''
|-
| align = "center"| [http://www.dolcera.com/website_prod/services/ip-patent-analytics-services Patent Analytics Services]
|align = "center"| [http://www.dolcera.com/website_prod/services/business-research-services Market Research Services]
|align = "center"| [http://www.dolcera.com/website_prod/tools/patent-dashboard Purchase Patent Dashboard]
|-
|align = "center"| [http://www.dolcera.com/website_prod/services/ip-patent-analytics-services/patent-search/patent-landscapes Patent Landscape Services]
|align = "center"| [http://www.dolcera.com/website_prod/research-processes Dolcera Processes]
|align = "center"| [http://www.dolcera.com/website_prod/industries Industry Focus]
|-
|align = "center"| [http://www.dolcera.com/website_prod/services/ip-patent-analytics-services/patent-search/patent-landscapes Patent Search Services]
|align = "center"| [http://www.dolcera.com/website_prod/services/ip-patent-analytics-services/alerts-and-updates Patent Alerting Services]
|align = "center"| [http://www.dolcera.com/website_prod/tools Dolcera Tools]
|-
|}
 

----
{| style="border:1px solid #AAA; background:#E9E9E9" align="center"
|-
! style="background:lightgrey" | Contact Dolcera
|-
! style="background:lightgrey" | Samir Raiyani
|-
| '''Email''': [mailto:info@dolcera.com info@dolcera.com]
|-
| '''Phone''': +1-650-269-7952, +91-40-2355-3493
|}

Drug Metabolism

2009-11-18T08:13:05Z

Tony.kurian@dolcera.com:

Yes up & working !