ABSTRACT
Cytochrome P450 (P450) binding is now widely recognized as a major focus for drug-drug interactions in the pharmaceutical industry. P450 metabolism-based drug-drug interactions, in vitro and in vivo, are routinely part of the product labeling and advertising copy, often in incomprehensible detail. P450s are ubiquitous throughout nature: they are present in bacteria, plants, and mammals, and there are hundreds of known enzymes that can show tissue- and species-specific expression. The pharmacokinetics of drug-drug interactions has been described; however, a number of points are worth briefly reiterating in the context of P450. P450 inhibitors can be readily identified by in vitro methods, and in the authors’ laboratories approximately 400 marketed drugs have been identified. From the pharmaceutical industry’s perspective, CYP1A2, CYP2C9, CYP2D6, and CYP3A4 address the overwhelming majority of the P450 issues and a little over 50% of the total target for pharmacokinetic drug-drug interaction studies.
