Novel Bioactivation Pathway of Benzbromarone Mediated by Cytochrome P450.

Cytochrome p450 architecture and cysteine nucleophile placement impact raloxifene-mediated mechanism-based inactivation.

The propensity for cytochrome P450 (P450) enzymes to bioactivate xenobiotics is governed by the inherent chemistry of the xenobiotic itself and the active site architecture of the P450 enzyme(s). Accessible nucleophiles in the active site or egress channels of the P450 enzyme have the potential of sequestering reactive metabolites through covalent modification, thereby limiting their exposure t...

Clopidogrel and proton pump inhibitors: a new drug interaction?

Clopidogrel is a thienopyridine platelet antagonist that irreversibly inhibits the binding of adenosine diphosphate to platelet receptors, ultimately leading to inhibition of platelet aggregation. Clopidogel is a prodrug requiring hepatic bioactivation via cytochrome P450 isozymes (CYP2C19, CYP3A4, CYP3A5) to its pharmacologically active form. Inhibition of cytochrome P450 may interfere with me...

Benzbromarone pharmacokinetics and pharmacodynamics in different cytochrome P450 2C9 genotypes.

Benzbromarone is a uricosuric drug and has been shown to be metabolized predominantly by cytochrome P450(CYP)2C9 in vitro findings. This study aims to investigate the influence of the CYP2C9 genotype on plasma levels of benzbromarone and 6-hydroxybenzbromarone, as well as uric acid lowering effects. A single oral dose pharmacokinetic and pharmacodynamic trial of benzbromarone (100 mg) was perfo...

A Novel Bioactivation Pathway for Diclofenac Initiated by P450-Mediated Oxidative Decarboxylation

Biotransformation of the anthraquinones emodin and chrysophanol by cytochrome P450 enzymes. Bioactivation to genotoxic metabolites.

The studies presented here were designed to elucidate the enzymes involved in the biotransformation of naturally occurring 1, 8-dihydroxyanthraquinones and to investigate whether biotransformation of 1,8-dihydroxyanthraquinones may represent a bioactivation pathway. We first studied the metabolism of emodin (1, 3,8-trihydroxy-6-methylanthraquinone), a compound present in pharmaceutical preparat...