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- W2061539226 abstract "Alfentanil undergoes extensive hepatic metabolism and exhibits a high degree of interindividual variability in hepatic clearance. The purpose of this investigation was to determine the specific hepatic cytochrome P450 isozyme(s) that catalyzes alfentanil metabolism. Alfentanil metabolism by microsomes from rat and human livers was determined by using gas chromatography-mass spectrometry. Rat liver alfentanil oxidation was increased threefold by treatment with pregnenolone 16 alpha-carbonitrile, an inducer of cytochrome P450 3A, but not by treatment with phenobarbital, beta-naphthoflavone, or pyrazole (which induce P450s 2B, 1A, and 2E1, respectively). Human liver microsomal alfentanil metabolism was correlated strongly with the content of cytochrome P450 3A3/4 (r = 0.85, P < 0.005), measured by Western blot analysis with a rabbit anti-human P450 3A3/4 probe. Alfentanil metabolism was diminished by the P450 3A3/4 substrate and competitive inhibitor midazolam, and was abolished by the specific P450 3A3/4 inhibitor troleandomycin. No other selective inhibitor of P450 isozymes (P450s 1A2, 2A6, 2C9/10, 2D6, 2E1) diminished alfentanil metabolism. These results establish that human alfentanil metabolism is catalyzed predominantly, if not exclusively, by P450 3A3/4. Interindividual variability in human alfentanil disposition and alfentanil drug interactions may be attributable to individual differences in P450 3A3/4 activity." @default.
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- W2061539226 date "1993-05-01" @default.
- W2061539226 modified "2023-10-10" @default.
- W2061539226 title "Human Alfentanil Metabolism by Cytochrome P450 3A3/4. An Explanation for the Interindividual Variability in Alfentanil Clearance?" @default.
- W2061539226 doi "https://doi.org/10.1213/00000539-199305000-00022" @default.
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