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首页> 外文期刊>Pharmacogenetics >Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes.
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Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes.

机译：成人中药物代谢酶的表型：体内细胞色素P450表型探针的综述。

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Cytochrome P450 phenotyping provides valuable information about real-time activity of these important drug-metabolizing enzymes through the use of specific probe drugs. Despite more than 20 years of research, few conclusions regarding optimal phenotyping methods have been reached. Caffeine offers many 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 information exists regarding their use, largely due to the narrow therapeutic index of most CYP2C9 probes. Mephenytoin has long been considered the standard CYP2C19 phenotyping probe, but problems such as sample stability and adverse effects have prompted the investigation of potential alternatives, such as omeprazole. Several well-validated CYP2D6 probes are available, including dextromethorphan, debrisoquin and sparteine, but, in most cases, dextromethorphan may be preferred due to its wide safety margin and availability. Chlorzoxazone remains the only CYP2E1 probe that has received much study. However, questions concerning phenotyping method and involvement of other enzymes have impaired its acceptance as a suitable CYP2E1 phenotyping probe. CYP3A phenotyping has been the subject of numerous investigations, reviews and commentaries. Nevertheless, much controversy regarding the selection of an ideal CYP3A probe remains. Of all the proposed methods, midazolam plasma clearance and the erythromycin breath test have been the most rigorously studied 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 resource.
机译：细胞色素P450表型分析通过使用特定的探针药物，提供了有关这些重要药物代谢酶的实时活性的有价值的信息。尽管进行了20多年的研究，但关于最佳表型分析方法的结论很少。咖啡因为CYP1A2表型提供许多优势，但广泛使用的咖啡因尿代谢比可能不是测量CYP1A2活性的最佳方法。已经提出了几种CYP2C9活性的探针，但是关于其使用的信息很少，这主要是由于大多数CYP2C9探针的治疗指数狭窄。长期以来，甲苯妥英一直被认为是标准的CYP2C19表型探针，但是诸如样品稳定性和副作用之类的问题促使人们研究了诸如奥美拉唑之类的潜在替代品。可以使用几种经过良好验证的CYP2D6探针，包括右美沙芬，右旋异喹啉和斯巴汀，但在大多数情况下，由于右美沙芬的安全性和实用性广，可能是首选。氯唑沙宗仍然是唯一受到许多研究的CYP2E1探针。然而，有关表型方法和其他酶参与的问题削弱了其作为合适的CYP2E1表型探针的接受性。 CYP3A表型已成为众多研究，评论和评论的主题。然而，关于理想的CYP3A探针的选择仍有许多争议。在所有提出的方法中，咪达唑仑血浆清除率和红霉素呼气试验已得到最严格的研究，并且似乎是可用方法中最可靠的方法。尽管许多当前可用的探针存在局限性，但随着不断的研究，表型化将成为更加有价值的研究和临床资源。

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