CYP2C9 polymorphisms: considerations in NSAID therapy.
The increased focus on safety in clinical trials represents a formidable hurdle regarding the availability of marketed drugs. The lengthy experimental process of ensuring the safety of a drug creates a need for faster, more efficient identification of drug toxicities. Profiling for individual genetic variability could be an essential screening process for potential adverse effects, especially within different ethnic populations. The identification of such variants should improve the management of patient care by, for example, identifying which patients should avoid a specific drug and which patients should be administered a modified dose. A suitable approach in implementing such a strategy could potentially reduce medical costs and improve the overall process and success of drug therapy. For example, polymorphisms in cytochrome P450 (CYP) 2C9, an enzyme involved in a variety of drug metabolisms, should be considered during future drug development of novel non-steroidal anti-inflammatory drugs (NSAIDs) because individuals with several variant alleles (eg, CYP2C9*2 and CYP2C9*3) have demonstrated decreased metabolic clearance compared with individuals with the wild-type enzyme (CYP2C9*1). The widespread use of NSAIDs, along with an increase in the occurrence of inflammatory diseases (such as arthritis) in aging populations, creates an incentive to consider CYP polymorphisms in treatment strategies.
Ali
Zaynah K
ZK
University of California, Berkeley, Department of Nutritional Sciences and Toxicology, CA 94720-3104, USA. pnapluza@berkeley.edu
Kim
Rebekah J
RJ
Ysla
Francis M
FM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D006801:Humans; D008657:Metabolic Clearance Rate; D010146:Pain / Q000188:drug therapy* / Q000201:enzymology; D011110:Polymorphism, Genetic; D011485:Protein Binding; D013379:Substrate Specificity
D000894:Anti-Inflammatory Agents, Non-Steroidal; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases