BACKGROUND 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. We have studied the effect of CYP2C9 polymorphism on the in-vivo wa...

A commercial Rhodiola rosea (R. rosea) product has previously demonstrated CYP2C9 inhibition in humans. The purpose of this study was to provide in vitro inhibitory data for this particular interaction and to classify the mechanism of the interaction. Another aim was to examine the in vitro influence of ethanol on the CYP2C9 activity. Human CYP2C9 (wild type) isolated from a baculovirus-infecte...

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...

CYP2C8 and CYP2C9 are involved in the inactivation of several non-steroidal anti-inflammatory drugs, including ibuprofen. CYP2C9 is the major form in human liver whereas CYP2C8 has been proposed to be the main CYP2C enzyme in fetal liver. The protein expression of CYP2C9 in the first trimester is low, only about 1% of the adult values, whereas the mRNA levels of CYP2C8/9 have not been determine...

Acetyl salicylic acid (ASA) is metabolized by UDP-glucuronosyltransferase 1A6 (UGT1A6), cytochrome P4502C9 (CYP2C9), and N-acetyl transferase 2 (NAT2). Variations in the activities of these enzymes may modulate adverse ASA-related symptoms such as urticaria. We examined whether polymorphisms in the UGT1A6, CYP2C9, and NAT2 genes are related to ASA-intolerant urticaria (AIU). The genotypes of 14...

Several reports suggest garlic supplements may inhibit the metabolism of cytochrome P450 (CYP) 2C9 and CYP3A4 substrates, such as warfarin and saquinavir. To characterize the effects of garlic extract on CYP2C9 and CYP3A4 enzyme activity immortalized human hepatocytes (Fa2N-4 cells) were exposed to garlic extract (0-200 μg/mL). CYP2C9 and CYP3A4 enzyme activities were evaluated in parallel with...

Noscapine is an antitussive and potential anticancer drug. Clinically significant interactions between warfarin and noscapine have been previously reported. In this study, to provide a basis for warfarin dosage adjustment, the inhibition kinetics of noscapine against warfarin metabolism was characterized. Our enzyme kinetics data obtained from human liver microsomes and recombinant CYP2C9 prote...

Fluorometric substrates selective for various cytochrome P450 isoforms (P450s) have great advantages in in vitro enzyme inhibition and induction studies because they are highly sensitive and suitable for rapid screening. 7-Methoxy-4-trifluoromethylcoumarin (MFC) has been reported as a CYP2C9-selective substrate. The present study investigated the relative catalytic selectivity of several human ...

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...