Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes

Cytochrome P450 phenotyping provides valuable information about real-time a ctivity of these important drug-metabolizing enzymes through the nse of spe cific probe drugs, Despite more than 20 years of research, few conclusions regarding optimal phenotyping methods have been reached. Caffeine offers ma ny advantages for CYP1A2 phenotyping, but the widely used caffeine urinary metabolic ratios may not be the optimal method of measuring CYP1A2 activity . Several probes of CYP2C9 activity have been suggested, but little informa tion exists regarding their use, largely due to the narrow therapeutic inde x of most CYP2C9 probes. Mephenytoin has long been considered the standard CYP2C19 phenotyping probe, but problems such as sample stability and advers e effects have prompted the investigation of potential alternatives, such a s omeprazole, Several well-validated CYP2D6 probes are available, including dextromethorphan, debrisoquin and sparteine, but, in most cases, dextromet horphan may be preferred due to its wide safety margin and availability. Ch lorzoxazone remains the only CYP2E1 probe that has received much study, How ever, questions concerning phenotyping method and involvement of other enzy mes have impaired its acceptance as a suitable CYP2E1 phenotyping probe. CY P3A phenotyping has been the subject of numerous investigations, reviews an d commentaries, Nevertheless, much controversy regarding the selection of a n ideal CYP3A probe remains. Of all the proposed methods, midazolam plasma clearance and the erythromycin breath test have been the most rigorously st udied and appear to be the most reliable of the available methods. Despite the limitations of many currently available probes, with continued research , phenotyping will become an even more valuable research and clinical resou rce. Pharmacogenetics 10:187-216 (C) 2000 Lippincott Williams & Wilkins.