CYP2C9 is an important human drug-metabolizing enzyme that is expressed primarily in liver. Recent studies in our laboratory have shown that the nuclear receptor pregnane X receptor (PXR) is important in the transcriptional activation of the CYP2C9 promoter by drugs such as rifampicin and that the essential element is a constitutive androstane receptor (CAR)/PXR site -1839 bp upstream of the tr...

References 1. Goldstein JA, de Morais SMF. Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics 1994;4:285–99. 2. Xie HG, Prasad HC, Kim RB, Stein CM. CYP2C9 allelic variants: ethnic distribution and functional significance. Adv Drug Deliv Rev 2002;54: 1257–70. 3. Linder MW. Genetic mechanisms for hypersensitivity and resistance to the anticoagulant warfarin. Clin C...

Cytochrome P450 enzymes from the CYP2C subfamily play a prominent role in the metabolic clearance of many drugs. CYP2C enzymes have also been implicated in the metabolism of arachidonic acid to vasoactive epoxyeicosatrienoic acids. CYP2C8, CYP2C9, and CYP2C19 are expressed in the adult liver at significant levels; however, the expression of CYP2C enzymes in extrahepatic tissues such as the brai...

OBJECTIVES Cytochrome P450 2C9 (CYP2C9) is a member of cytochrome P450 (CYP) family that accounts for nearly 18% of the total CYP protein content in the human liver microsomes and catalyzes almost 15-20% of the drugs. Considering the paucity of data on the polymorphisms of CYP2C9 in Western Indian population, the present study was conducted to evaluate the prevalence of CYP2C9 polymorphisms (*1...

To evaluate the inhibitory effects of trimethoprim and sulfamethoxazole on cytochrome P450 (P450) isoforms, selective marker reactions for CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 were examined in human liver microsomes and recombinant CYP2C8 and CYP2C9. The in vivo drug interactions of trimethoprim and sulfamethoxazole were predicted in vitro using [I]/([I] + K(i)) v...

Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genetic polymorphisms were strongly associated with warfarin dose requirement in Caucasians, African Americans and other populations. Our aim was to evaluate the effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirement in south Indian population. A total of 150 patients on warfarin with...

CYP2C enzymes are expressed constitutively and comprise approximately 20% of the total cytochrome P450 in human liver. However, the factors influencing the transcriptional regulation of the CYP2C subfamily have only been addressed recently. In the present study, we used primary cultures of human hepatocytes to investigate the role of HNF4alpha in the pregnane X receptor (PXR)/rifampicin-mediate...

CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate s...

PURPOSE The aim of this study was to clarify the effects of genetic polymorphisms of cytochrome P450 (CYP) 2C9 and 2C19 on the metabolism of phenytoin (PHT). In addition, a population pharmacokinetic analysis was performed. METHODS The genotype of CYP2C9 (Arg144/Cys, Ile359/Leu) and CYP2C19(*1, *2 or *3) in 134 Japanese adult patients with epilepsy treated with PHT were determined, and their ...