Stereoselective and isozyme-selective drug interactions.
A surprisingly large number of marketed drugs are racemic mixtures. The pharmacokinetic literature on racemic drugs contains a vast amount of information on drug-drug interactions derived from the measurement of total drug concentrations in plasma and urine. The appreciation of the role of stereochemistry in drug interactions with racemic warfarin resulted in a long-overdue scientific rigor being applied to the study of drug interactions. It also compelled us to recognize that much of the literature was uninterpretable. A better understanding of oxidative metabolism, particularly the complexity of the cytochrome P-450 family of enzymes, has also strengthened the scientific basis of drug interactions. We now recognize that investigators and clinicians must consider both stereoselectivity and isozyme selectivity in the study of drug interactions to understand the nature of the interaction so as to more effectively use new and potent drugs.
School of Pharmacy, University of Washington, Seattle 98195.
M
M
Gibaldi
D002927:Cimetidine / Q000008:administration & dosage; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011802:Quinidine / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D013237:Stereoisomerism; D014859:Warfarin / Q000008:administration & dosage
D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D014859:Warfarin; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D011802:Quinidine; D012293:Rifampin