The market withdrawals of rofecoxib (Vioxx) and valdecoxib (Bextra) have focused considerable attention on the side effect profiles of cyclooxygenase (COX) inhibitors. As a result, attempts will be made to identify risk factors in the hope that physicians might be able to ensure patient safety. At first glance, CYP2C9 genotype might be considered a risk factor because many COX inhibitors are CY...

Olanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions. Currently, there are no clinical guidelines implementing pharmacogenetic information on olanzapine. Moreover, Dutch Pharmacogenomics Working Group (DPWG) states that CYP2D6 phenotype not related to olanzapine response or side effects. Thus, objective this ca...

215 words Introduction: 1170 words Main text: 5045 words Conclusions: 390 words References: 98 Number of tables: 1 This article has not been copyedited and formatted. The final version may differ from this version. DMD Fast Forward. Published on August 23, 2005 as DOI: 10.1124/dmd.105.006452 at A PE T Jornals on Jne 0, 2017 dm d.aspurnals.org D ow nladed from DMD 6452 (Revised) 3 Abbreviations:...

Cytochrome P4502C9 (CYP2C9) is an important drug-metabolizing enzyme responsible for the metabolism of approximately 16% of all clinically relevant drugs. It was shown previously that the activity of CYP2C9 in vivo is inhibited by oral contraceptives. The mechanisms of this effect have not been elucidated. We hypothesize that this may occur because of the sex steroid-dependent activation of est...

Previous studies in our laboratory showed that among cDNA-expressed human cytochrome P450 (P450) supersomes, CYP2C19 was the most active in methoxychlor-O-demethylation. However, based on the lack of inhibition of methoxychlor-O-demethylation by monoclonal anti-CYP2C19 antibodies in human liver microsomes (HLM), CYP2C19 did not seem to catalyze that reaction in HLM. By contrast, CYP2C9, much le...

BACKGROUND AND OBJECTIVES Phenytoin, a widely used anti-epileptic drug, is metabolized mainly by CYP2C9 (90%) and partly by CYP2C19 (10%) to its major metabolite 5-(para-hydroxyphenyl)-5- phenylhydantoin (p-HPPH). The CYP2C9 and CYP2C19 genes encoding these enzymes are polymorphically expressed and most of the variants result in decreased metabolism of the respective substrates. The present stu...

CYP2C9 is one of the major drug-metabolizing enzymes, and it is involved in the oxidative metabolism of approximately 10% of clinically important drugs, among which some, such as the anticoagulant warfarin, have a narrow therapeutic index. The human CYP2C9 gene is highly polymorphic. We found a new sequence variation in exon 7 of the CYP2C9 gene (1060G>A) resulting in a substitution of acidic a...