The anticoagulant drug warfarin occurs as a pair of enantiomers that are differentially metabolized by human cytochromes P450 (CYP). R-warfarin is metabolized primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by CYP3A4 to 10-hydroxywarfarin, and by carbonyl reductases to diastereoisomeric alcohols.S-warfarin is metabolized primarily by CYP2C9 to 7-hydroxywarfarin This study investigated warfarin dose and INR response following CYP-inducing anticonvulsant initiation among chronic warfarin users. This retrospective, pre-post study included patients ≥18 years who were receiving chronic warfarin therapy and who initiated carbamazepine, oxcarbazepine, phenobarbital, or phenytoin between January 1, 2006. Attention should be paid to the relative importance of the warfarin cytochrome P450 (CYP) metabolic pathways. Warfarin is a racemic mixture of its R-isomer (less potent) and S-isomer (more potent. Warfarin is metabolized by the hepatic Cytochrome P450 system. A long list of drugs can interact with this system, either by inducing increased synthesis of P450 and thus enhanced metabolism of warfarin, or by interfering with P450 metabolism of warfarin and thus increasing its blood concentration
Genetic Variant Information. The CYP2C9 (sounds like sip-2-see-9) gene encodes the CYP2C9 enzyme, which is a member of the cytochrome P450 enzyme family. There are different CYP2C9 gene versions, or variants, and each has a different effect on how well warfarin is metabolized in the body. Some variants result in a non-functioning or low-functioning CYP2C9 protein while other variants. Delta-9-tetrahydrocannabinol (THC), the main psychoactive cannabinoid in cannabis, may inhibit the cytochrome P450 enzyme CYP2C9. Consequently, cannabis use might infer a risk of drug-drug interaction with substrates for this enzyme, which includes drugs known to have a narrow therapeutic window. In s účastí cytochromů P450(17). Antikoagulancia - warfarin Preparáty warfarinu obsahují dva diastereomery, R-warfarin a S-warfarin. Oba jsou účinné, účinnost R-warfarinu je však jen 30 % ve srovnání s S-enantiomerem. Na jeho metabolizmu se podílí několik forem cytochromu P450: CYP2C9 přeměňuj Warfarin se užívá většinou jednou denně, pokud možno vždy ve stejnou dobu. Dávka je individuální a určuje ji lékař. Jestliže jste zapomněl(a) užít jednu dávku a uvědomíte si to během 12 hodin, můžete si vzít zapomenutou dávku ihned. Další dávku užijte jak jste zvyklý(á) Lidé léčení warfarinem, lékem na ředění krve, a dalšími léky se stejnou účinnou látkou musejí kontrolovat příjem vitaminu K, který je obsažen zejména v listové a košťálové zelenině. Účinnost warfarinu ovlivňují potraviny, doplňky stravy a léky
Cytochrome P450 inducers Reduce the concentration of drugs metabolised by the cytocrome P450 system. Mnemonic: CRAPS out drugs C arbamazepine . R. ifampicin . b. A. rbituates . P. henytoin . S. t Johns wort . Cytochrome P450 inhibitors . Increase the concentration of drugs metabolised by the cytocrome P450 system. Mnemonic: S. ome C ertain S. Pharmacokinetic interactions with warfarin can alter its absorption, distribution, or elimination. Interactions affecting warfarin metabolism are the most susceptible to genetic influence. Specifically, several cytochrome P450 (CYP450) enzymes, including CYP2C9, CYP3A4, CYP1A2, and CYP2C19, contribute to the elimination of warfarin Interactions with warfarin, antidepressants, antiepileptic drugs, and statins often involve the cytochrome P450 enzymes. Knowledge of the most important drugs metabolized by cytochrome P450.
R-warfarin zaleplon zileuton zolpidem zonisamide: CYP2C9: amiodarone cimetidine cortrimoxazole fluconazole ***fluvoxamine isoniazid ketoconazole metronidazole zafirlukast: barbiturates carbamazepine rifampin rifapentine St. John's wort: carvedilol celecoxib diclofenac flurbiprofen fluvastatin glimepiride ibuprofen irbesartan losartan. Odpovědi na Vaše dotazy týkající se užívání léku Warfarin. Účinek Warfarinu negativně ovlivňuje vitamin K, ale také vysoké dávky vitaminu C. Plody jeřábu černého (aronie) jsou velmi bohaté na vitamin C a zatím nejsou studie, které by prokázaly nebo vyvrátily jeho negativní účinek na Warfarin
Rifampicin remains one of the first-line drugs used in tuberculosis therapy. This drug´s potential to induce the hepatic cytochrome P450 oxidative enzyme system increases the risk of drug-drug interactions. Thus, although the presence of comorbidities typically necessitates the use of multiple drugs, the co-administration of rifampicin and warfarin may lead to adverse drug events Type a medicine into the Drug Name box and hit return; you get lots of technical data, but effects on cytochrome p450 are listed halfway down under 'CYP interactions'. Quick clinical question When checking an interaction, you discover that rifampicin induces the metabolism of warfarin via CYP 3A4
Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken. Kensuke P. Watanabe. Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan The cytochrome P450 CYP2C9 is responsible for the metabolism of S-warfarin. Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single aminoacid substitution in each case. The allelic variants are associated with impaired hydroxylation of S-warfarin in in-vitro expression systems The molecular basis of drug recognition by human CYP450s, however, has remained elusive. Here we describe the crystal structure of a human CYP450, CYP2C9, both unliganded and in complex with the anti-coagulant drug warfarin. The structure defines unanticipated interactions between CYP2C9 and warfarin, and reveals a new binding pocket cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999;353:717-9. 3 Taube J, Halsall D, Baglin T. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 2000;96:1816-9. 4 FitzGerald GA, Patrono C the interaction is biologically plausible because cranberry juice contains various antioxidants including flavonoids, which are known to inhibit cytochrome P450 activity, and warfarin is predominantly metabolised by the P450 isoform CYP2C
HELP US GET OUR OWN FILMING STUDIO -- https://www.gofundme.com/f/ninja-nerd-science Ninja Nerds, Join us for our Pharmacology lecture on Warfarin. During thi.. 2C9 (and to a lesser degree by P450 3A4) and is eliminated in the bile. The R-isomer, in contrast, is primarily metabolized by cytochrome P450 1A2 and P450 3A4 and is excreted in the urine as inactive metabolites. Since the S-isomer is much more potent than the R-isomer , medications that inhibit or induce the P450 2C9 pathway lead to th
Estimates are based on clinical factors and (when available) genotypes of two genes: cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1). Recommendations on this Web site are based on data from over 1000 patients The well established and clinically important anticoagulant drug S-warfarin is a typical human P450 2C9 substrate (Yamazaki and Shimada, 1997). Cynomolgus monkey P450 2C19 has high activity toward R-warfarin 7-hydroxylation (Hosoi et al., 2012), whereas marmoset P450 2C19 efficiently catalyzes S-warfarin 7-hydroxylation (Uehara et al., 2015) Warfarin is an anticoagulant available as a racemic mixture. The R‐ and S‐isomers differ with respect to relative plasma concentrations, clearance, potency, sites of metabolism, and cytochrome P450 (CYP) isoenzymes responsible for metabolism. S‐Warfarin, the more potent isomer, is metabolized primarily by CYP2C9 Aim. To assess the effect of Cytochrome P450 2C9 (CYP 2C9) gene polymorphism on pediatric warfarin maintenance dosage requirement.. Methods. A previously developed search strategy was conducted in PubMed, EMBASE , and the Cochrane Library. Eligible studies published prior to January 27, 2016, were identified and compared against strict inclusion/exclusion criteria
P450 isozymes metabolizing R/S warfarin is similar to that metabolizing R/S acenocoumarol, the inhibiting effects of four drugs (cimetidine, propafenone, sulphaphenazole, and omeprazole) have been studied. Cimetidine and omeprazole were chosen since these compounds are known to decrease the clearance of R-warfarin in man (Choonara et al., 1986 The mechanism is understood to be inhibition by miconazole of one of the main cytochrome P450 isozymes involved in warfarin metabolism (CYP2C9), resulting in reduced warfarin clearance and an.
Warfarin is commonly used in general practice to treat and prevent thrombosis in a range of clinical settings. It acts by antagonising the action of vitamin K resulting in production of defective clotting proteins. It is cleared via the cytochrome P450 enzymes in the liver and is subject to interactions with a large number of drugs R-Warfarin: Caffeine: Sitemap. Pharmacy Law and Ethics General Pharmaceutical Council Guidance Royal Pharmaceutical Society Guidance PSNI Code of Ethics, Standards and Guidance Medicines, Ethics and Practice Prescriptions Controlled Drugs Supplementary and Independent Prescribing and PGD
Table 3-3: Examples of clinical inducers for P450-mediated metabolisms (for concomitant use clinical DDI studies and/or drug labeling) (12/03/2019) Strong inducers Moderate inducer
The superfamily of proteins called cytochrome P450 (CYP) enzymes are involved in the synthesis and metabolism of a range of internal and external cellular components. These enzymes have been. Inducer, e.g. rifampicin = a drug that stimulates the production of a CYP450 enzyme, e.g. CYP2C19. If a drug, e.g. warfarin is metabolised (into an inactive compound) by this enzyme, then warfarin will be metabolised more quickly under the influence of rifampicin
between warfarin and amiodarone results in an increased warfarin effect. There are several large, well-performed studies using genetic and clinical factors such as co-medi-cation to predict an adequate starting dose of warfarin. However, longitudinal data on the effect of introducing amiodarone in patients on an ongoing warfarin regime are more. Both S-warfarin and R-warfarin are metabolized by cytochrome P450 (CYP) enzymes (a group of intestinal and liver enzymes responsible for drug metabolism). Metronidazole's metabolism and its specific effect on warfarin are not as clearly defined. Metronidazole has been reported to have a stereoselective inhibition of S-warfarin metabolism which. CD and UC Participants: Apparent Volume of Distribution (Vz/F) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine) [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 (only for dextromethorphan and S-warfarin), 72 (only for S-warfarin) and 96 hours (only for S-warfarin) on Days. Genetic factors most correlated with warfarin dose requirements are variations in the genes encoding the enzymes cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR). Patients receiving warfarin who possess one or more genetic variations in CYP2C9 and VKORC1 are at increased risk of adverse drug events and require significant dose reductions to achieve a therapeutic.
Induction or inhibition of cytochrome P450 isozymes Warfarin has 2 active isomers.1 The S-isomer is approximately 2 to 4 times more potent than the R-isomer and is metabolized primarily by the cyto-chrome P450 2C9 isozyme (CYP2C9). The R-iso-mer is metabolized by cytochrome P450 1A2 and 3A4 isozymes. Drugs that induce or inhibit thes Cannabidiol is a safe, non-intoxicating, and non-addictive cannabis compound with significant therapeutic attributes, but CBD-drug interactions may be problematic in some cases.. CBD and other plant cannabinoids can potentially interact with many pharmaceuticals by inhibiting the activity of cytochrome P450, a family of liver enzymes.This key enzyme group metabolizes most of the drugs we. The human body uses cytochrome P450 enzymes to process medications. Because of inherited (genetic) traits that cause variations in these enzymes, medications may affect each person differently. Drug-gene testing — also called pharmacogenomics or pharmacogenetics — is the study of how genes affect your body's response to medication Genetic predisposition to warfarin resistance related to an increase in metabolic clearance has been reported in a patient who required a daily warfarin dose of 60 mg.4 Warfarin metabolism is catalyzed by cytochrome P450 (CYP) 2C9, which metabolizes S-warfarin to inactive S-7-hydroxywarfarin.5Polymorphisms in the coding region of the CYP2C9gene with variants at 416CGT>TGT (Arg144Cys) in exon 3. In vitro evaluation of valproic acid as an inhibitor of human cytochrome P450 isoforms: preferential inhibition of cytochrome P450 2C9 (CYP2C9). Br J Clin Pharmacol 2001 Nov;52(5):547-53
Marmoset P450 2C proteins were detected in liver by immunoblotting using antibodies against human P450 2Cs. Among marmoset P450 2Cs heterologously expressed in Escherichia coli , marmoset P450 2C19 efficiently catalyzed human P450 2C substrates, S -warfarin, diclofenac, tolbutamide, flurbiprofen, and omeprazole Human P450 metabolism of warfarin. Pharmacology & Therapeutics 1997, 73 (1) , 67-74. DOI: 10.1016/S0163-7258(96)00140-4. F. Peter Guengerich. Role of Cytochrome P450 Enzymes in Drug-Drug Interactions. 1997, 7-35. DOI: 10.1016/S1054-3589(08)60200-8. Patrick Maurel. The use of adult human hepatocytes in primary culture and other in vitro. Cytochrome P450 2D6 Known Drug Interaction Chart Drugs Metabolized by CYP2D6 Enzyme Drug Inhibitors of CYP2D6 Enzyme ANALGESICS CHOLINESTERASE INHIBITORS STRONG INHIBITORS OTHER KNOWN INHIBITORS:* codeine donepezil bupropion ANALGESICS hydrocodone cinacalcet celecoxib oxycodone COUGH SUPPRESSANT fluoxetine methadon
The anticoagulant drug warfarin occurs as a pair of enantiomers that are differentially metabolized by human cytochromes P450 (CYP). R-warfarin is metabolized primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by CYP3A4 to 10-hydroxywarfarin, and by carbonyl reductases to diastereoisomeric alcohols. S-warfarin is metabolized primarily by CYP2C9 to 7-hydroxywarfarin Cytochrome P450 2C9 (CYP2C9) metabolizes many clinically important drugs including warfarin and diclofenac. We have recently reported a new allelic variant, CYP2C9*35, found in a warfarin. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599)
CBD, in turns out, is a more potent inhibitor of cytochrome P450 enzymes than the grapefruit compound Bergapten (the strongest of several grapefruit components that inhibit CYPs) Cytochrome P450 Drug Interactions Lead authors: Terri L. Levien, R.Ph., and Danial E. Baker, Pharm.D., FASCP, FASHP (Last Updated May 2003-See newly added CYP2C8 category on page 4) The characterization of drug interactions by metabolic pathways is complex. Just because a medication interacts with on Warfarin/courmarins† However, for pravastatin (Lipostat), which is not metabolised by cytochrome P450, warfarin interaction is less of a concern. Fibrates
¾Warfarin pharmacogenetics meets clinical use ¾M. Schwab, E. Schaeffer, Blood 118, 2938-2939 (2012) ¾I. Y. Gong et al, Blood 118, 3163-3171 (2012) Algoritmus WRAPID, pro počáteční dávkování WRAPID = Warfarin Regimen using A Pharmacogenetics-guided Initiation Dosing 167 pacientů, Atriální fibrilace a žilní tromboemboli The structure defines unanticipated interactions between CYP2C9 and warfarin, and reveals a new binding pocket. The binding mode of warfarin suggests that CYP2C9 may undergo an allosteric. 1 Faculty of Chemical Sciences, Benemérita Universidad Autónoma de Puebla, CP 72570 Puebla, State Puebla, Mexico . 2 Center for Biosystem Analysis ZBSA, University of Freiburg, Freiburg, Germany *Correspondence to: Thomas Scior, E-mail: firstname.lastname@example.org Citation: Scior T, Quiroga- Montes I, Kammerer B (2018) Inquiry of Literature Evidence for Induced Fit of Cytochrome P450 2C9 for Warfarin. Please use one of the following formats to cite this article in your essay, paper or report: APA. Simmons, Hannah. (2019, February 26). Que são enzimas do citocromo (CYP) P450?
Though natural, herbs can still pose medication interactions. There have actually been very few reported interactions between chamomile and over-the-counter or prescription drugs, but the most significant ones are related to use of the herb with Coumadin (warfarin)—a common blood thinner—and cyclosporine—a drug used to prevent rejection after organ transplantation Small intestinal cytochromes P450 (P450s) provide potential first-pass metabolism of ingested xenobiotics. To investigate this system, this study addresses the procedure for elution of enterocytes from male rat small intestine, histological evaluation of the elution procedure, and assessment of the functional microsomal P450s in small intestine of untreated and induced rats, using warfarin. An anti-p450 2a-5 antibody did not consistently inhibit any of the warfarin biotransformation reactions catalyzed by human or mouse liver microsomes although coumarin 7-hydroxylation was inhibited by over 90%. In some human microsomal samples 4- and 8-hydroxylations of warfarin were inhibited to some extent by the anti-p450 2a-5 antibody
Various drug databases can provide information about cytochrome P450 inhibitors. [ 21 , 22 , 23 ] Major interactions should be avoided, especially for short duration therapies, and replaced with. Human P450 metabolism of warfarin. Pharmacology & Therapeutics 1997, 73 (1) , 67-74. DOI: 10.1016/S0163-7258(96)00140-4. F. Peter Guengerich. Role of Cytochrome P450 Enzymes in Drug-Drug Interactions. 1997, 7-35. DOI: 10.1016/S1054-3589(08)60200-8. Patrick Maurel. The use of adult human hepatocytes in primary culture and other in vitro. Laboratory studies have shown that pomegranate juice inhibits key cytochrome P450 enzymes involved in warfarin metabolism and thereby provide a mechanistic explanation for this potential interaction.2 Warfarin is composed of two enantiomers, R-warfarin and S-warfarin. R-warfarin is metabolised primarily by CYP1A2 to 6- and 8-hydroxywarfarin, by. Warfarin is almost entirely metabolised in the liver by the hepatic cytochrome P450 enzymes (CYP1A2, CYP3A4, CYP2C9) and numerous drug interactions have been documented with it. Pharmacokinetic metabolism interactions with induction and inhibition of the cytochrome P450 enzyme subtypes is a frequent mechanism of interaction, resulting in low.
Warfarin is available as a racemic mixture of two R-and S-enantiomers. The clinical effect of warfarin relies mainly on S-warfarin, which is pharmacologically more active than R-warfarin. S-warfarin is mainly hydroxylated by the cyto-chrome P450 2C9 (CYP2C9) enzyme to 7-hydroxywarfarin1,2. Recent pharmacogeneti The cytochrome P450 enzymes may be inhibited by a variety of mechanisms [9, 12, 13] such as simple competition for substrates for cytochrome P450 (quinidine, sulfaphenazole), compounds that bind to the haem (cimetidine), theophylline and warfarin Pharmacology Mnemonics The best medication mnemonics for medical student finals, OSCEs and MRCP ACE inhibitor side effects (CAPTOPRIL) Cough Angioneurotic oedema Proteinuria Taste disturbance/ Teratogenic in 1st trimester Other (fatigue, headache) Potassium increased Renal impairment Itch Low BP (1st dose) Beneficial effects of inhibition of prostaglandin synthesis i.e. paracetamol and NSAIDs. Many factors influence the metabolism of warfarin, including disease states, medications, age, and diet. Data collected in this case suggested clarithromycin may have contributed to the increase in the effect of warfarin. Inhibition of the cytochrome P450 oxidizing system appears to be the reason for the increase
Warfarin is one of the most widely prescribed oral anticoagulants. However, optimal use of the drug has been hampered by its >10-fold interpatient variability in the doses required to attain therapeutic responses. Pharmacogenetic polymorphism of cytochrome P450 (CYP) may be associated with impaired elimination of warfarin and exaggerated anticoagulatory responses to the drug in certain patients Cytochrome P450 3A4 and 3A5 Known Drug Interaction Chart CYP3A4 and CYP3A5 Substrates. CYP3A4 and CYP3A5 Inhibitors: ANTIHISTAMINES NEUROPSYCHIATRIC STRONG INHIBITORS: astemizole: alprazolam clarithromycin: chlorpheniramine. diazepam; indinavir. ANTIMETRIC. midazolam itraconazole aprepitant. triazolam ketoconazole. ondansetron Dietary factors may affect the action of warfarin and the resultant INR. Deficiency of vitamin K will increase the INR, while a diet high in vitamin K will decrease it. Dietary substances that inhibit or induce the cytochrome P450 pathway may alter warfarin's metabolism and increase or decrease its half-life Drug Interaction Classification Systems: Significance Rating (A) Criteria Management Rating (B) Criteria: 0: Not listed 0: Not listed: 1: Severity - Major: The effects are potentially life-threatening or capable of causing permanent damage. Documentation: interaction is suspected, probable or established
Statisticians: Elena Deych, MS, co-developed the warfarin initiation algorithms on WarfarinDosing.org. Petra Lenzini, MS, co-developed the warfarin refinement algorithms on WarfarinDosing.org. Technicians & Laboratory Managers: Cristi King, BS, and Rhonda Porche-Sorbet, MS, are responsible for the cytochrome P450 2C9 and VKORC1 and other. Drug metabolism may be perturbed by genetically determined differences in the metabolic activity of cytochrome P450 enzymes. The authors encountered extensive bleeding in a patient receiving warfarin for anticoagulation after the introduction of celecoxib, an anti-inflammatory drug The asymmetric carbon of warfarin (C9) gives rise to two enantiomeric forms, R-warfarin and S-warfarin, which are differentially metabolised. When administered as a racemate, S-warfarin is about three times as potent as R-warfarin.8 The cytochrome P450 CYP2C9 is the principal enzyme that catalyses the conversion of S 1. Aithal GP, Day CP, Kesteven PJ, Daly AK: Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications Michalets EL. Update: clinically significant cytochrome P450 drug interaction. Pharmocotherapy 1998,18(1):84-112. Levien TL., Baker DE. Cytochrome P450 drug interaction. Pharmacist's Letter 1999 Document No.:150400. North DS, Weiss M, Mullen WJ. Pharmaceuticals and the cytochrome P450 isoenzymes: A tool for decision making
The anticoagulant effect of warfarin is due to the inhibition of the vitamin K-dependent epoxide reductase enzyme, leading to a reduction of the vitamin K pool and an inability to activate the vitamin K-dependent clotting factors. The active component of warfarin is metabolized by cytochrome P450 2C9 (CYP2C9) Warfarin use is complicated by an erratic dose response. Interpatient variability associated with warfarin therapy may be partly attributable to polymorphisms of the cytochrome P450 (CYP) complex. The purpose of this study was to ascertain the frequency and influence of CYP polymorphisms on warfarin dosing in our patient population. Methods Cytochrome P450 monooxygenases: an update on perspectives for synthetic application Vlada B. Urlacher and Marco Girhard Institute of Biochemistry, Heinrich-Heine-Universita¨tDu¨sseldorf, Universita¨tsstraße 1, D-40225 Du¨sseldorf, German
This study aimed to evaluate the effect of cytochrome P450 2C9 isoform (CYP2C9) polymorphism on the dosage variability and therapeutic efficacy of warfarin in a subset of Saudi patient. Materials and Methods: The study included 112 patients on regular warfarin therapy for various causes warfarin) происходит от аббревиатуры WARF (англ. Wisconsin Alumni Research Foundation) + окончание -arin, указывающее на связь с кумарином. Варфарин вначале был зарегистрирован как яд для грызунов в США в 1948 году и. Reports of an interaction between warfarin and acetaminophen first appeared in the literature in 1968. 5 Acetaminophen is part of the class of drugs known as aniline analgesics; it is the only such drug still in use today. 6 Acetaminophen is used worldwide as an analgesic and antipyretic. Because aspirin and other nonsteroidal anti-inflammatory drugs inhibit platelet function and can.
The antibacterial agent linezolid would not be expected to participate in drug-drug interactions via the cytochrome P450 (CYP) system because it does not appear to be a substrate, inhibitor, or inducer of such isozymes. Warfarin is metabolized by several CYP isozymes, with CYP2C9 being the most important Human liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol: P450 isozyme diversity determines the differences in their pharmacokinetics J.J.R. Hermans Cardiovascular Research Institute Maastricht, Department of Pharmacology, University of Limburg, PO Box 616, 6200 MD Maastricht, The Netherland Article Citation: Dorothy M. Adcock, Charles Koftan, Domnita Crisan, and Frederick L. Kiechle (2004) Effect of Polymorphisms in the Cytochrome P450 CYP2C9 Gene on Warfarin Anticoagulation. Archives of Pathology & Laboratory Medicine: December 2004, Vol. 128, No. 12, pp. 1360-1363 warfarin sensitivity Certain common CYP2C9 gene variations (polymorphisms) that decrease the activity of the CYP2C9 enzyme can result in a condition called warfarin sensitivity. The altered enzyme slows the breakdown (metabolism) of warfarin, allowing the drug to remain active in the body for a longer period of time However, there may be one side effects to keep in mind, which is the inhibition of the cytochrome p450 enzyme system. By inhibiting the cytochrome p450 system, it may lead to an overall increase in the processing of the other drugs in your system. Thus the other drugs may not metabolize as they should