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Assessment of cytochrome P450 activity by a five‐drug cocktail approach
Author(s) -
Zhu Bing,
OuYang DongSheng,
Chen XiaoPing,
Huang SongLin,
Tan ZhiRong,
He Nan,
Zhou HongHao
Publication year - 2001
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(01)92726-2
Subject(s) - chlorzoxazone , mephenytoin , pharmacology , cyp2d6 , cyp3a , metoprolol , cyp1a2 , cyp2c19 , tolbutamide , caffeine , midazolam , paraxanthine , drug interaction , chemistry , dextromethorphan , drug , medicine , cyp2e1 , cytochrome p450 , biochemistry , metabolism , insulin , sedation
Objectives Our goal was to establish and validate a modified cocktail approach including probe drugs caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam for simultaneous phenotyping of CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A. Methods The study was conducted in 14 healthy, nonsmoking male volunteers with a cocktail of 5 drugs consisting of 100 mg caffeine, 200 mg chlorzoxazone, 100 mg mephenytoin, 100 mg metoprolol, and 7.5 mg midazolam in a randomized manner with a 7 × 7 Latin square design. Plasma was obtained at 1, 4, and 6 hours, and urine was collected from 0 to 8 hours after oral drug administration. Results The phenotypic indexes determined for caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam were not significantly different when the drugs were given in different combinations. There were no metabolic interactions or analytic interference of these probe drugs. Conclusions This cocktail approach can simultaneously provide independent in vivo phenotypic measures for the cytochrome P450 (CYP) enzymes CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A. Clinical Pharmacology & Therapeutics (2001) 70 , 455–461; doi: 10.1016/S0009‐9236(01)92726‐2