Comment
Author: Admin | 2025-04-28
With one wild-type and one variant allele have reduced enzyme activity. Finally, some persons inherit multiple copies of wild-type alleles, which results in excess enzyme activity. This phenotype is termed an “ultrarapid” metabolizer.4 CYP450 enzyme polymorphism is responsible for observed variations in drug response among patients of differing ethnic origins.4–6 For example, 7 percent of white persons and 2 to 7 percent of black persons are poor metabolizers of drugs dependent on CYP2D6, which metabolizes many beta blockers, antidepressants, and opioids.7,8 One in five Asian persons is a poor metabolizer of drugs dependent on CYP2C19, which metabolizes phenytoin (Dilantin), phenobarbital, omeprazole (Prilosec), and other drugs.9 Variance in drug response among persons of different ethnic origins also can be caused by genetic variations in other drug-metabolizing enzymes, drug transporters, and drug receptors.3 Many drug interactions are the result of an alteration of CYP450 metabolism.10 The non-sedating antihistamines terfenadine (Seldane) and astemizole (Hismanal), and the gastrointestinal motility agent cisapride (Propulsid), were all withdrawn from the U.S. market because metabolic inhibition by other drugs led to life-threatening arrhythmias.11 The calcium channel blocker mibefradil (Posicor) was withdrawn from the U.S. market in 1998 because it was a potent enzyme inhibitor that resulted in toxic levels of other cardiovascular drugs.12 Drugs interact with the CYP450 system in several ways. Drugs may be metabolized by only one CYP450 enzyme (e.g., metoprolol by CYP2D6) or by multiple enzymes (e.g., warfarin [Coumadin] by CYP1A2, CYP2D6, and CYP3A4).13 Drugs that cause CYP450 metabolic drug interactions are referred to as
Add Comment