In vivo effect of clarithromycin on multiple cytochrome P450s.
In vivo effect of clarithromycin on multiple cytochrome P450s.
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发表时间：
2001-07
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通讯作者：
M. Bruce;S. Hall;B. Haehner‐Daniels;J. Gorski
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作者：
M. Bruce;S. Hall;B. Haehner‐Daniels;J. Gorski
测定口服克拉霉素对细胞色素 P450 1A2、2C9 和 2D6 体内活性的体内影响。 12 名健康男性受试者在口服克拉霉素（500 mg，每日两次）之前和之后 7 天，以口服鸡尾酒形式施用细胞色素 P450 探针咖啡因 (CYP1A2)、甲苯磺丁脲 (CYP2C9) 和右美沙芬 (CYP2D6)。收集血液和尿液样本，并使用高效液相色谱法分析每种化合物及其代谢物。服用克拉霉素后，CYP1A2 指数、口服咖啡因清除率（治疗前 6.2 +/- 3.3 l/h，治疗后 5.7 +/- 4.2 l/h，p > 0.05）和 6 小时副黄嘌呤与咖啡因血清浓度比（治疗前 0.49 +/- 0.3，治疗后 0.44 +/- 0.3，p > 0.05）没有变化。剂量。服用克拉霉素均未改变甲苯磺丁脲口服清除率（之前 0.77 +/- 0.28 l/h，之后 0.72 +/-0.24 l/h，p > 0.05）和甲苯磺丁脲尿代谢比（之前 779 +/- 294，之后 681 +/- 416，p > 0.05）CYP2C9 指数。就 CYP2D6 而言，克拉霉素给药前 (0.021 +/- 0.04) 和给药后 (0.024 +/- 0.06) 尿右美沙芬与右啡烷比率没有显着差异。总之，根据咖啡因、甲苯磺丁脲和右美沙芬的评估，克拉霉素似乎不会改变健康个体中 CYP1A2、CYP2C9 和 CYP2D6 的体内催化活性。
The in vivo effects of oral clarithromycin administration on the in vivo activity of cytochrome P450 1A2, 2C9, and 2D6 were determined. The cytochrome P450 probes caffeine (CYP1A2), tolbutamide (CYP2C9), and dextromethorphan (CYP2D6) were administered as an oral cocktail prior to and 7 days after oral clarithromycin (500 mg twice daily) administration to 12 healthy male subjects. Blood and urine samples were collected and assayed for each of the compounds and their metabolites using high-performance liquid chromatography. The CYP1A2 indices, oral caffeine clearance (6.2 +/- 3.3 l/h before and 5.7 +/- 4.2 l/h after, p > 0.05) and the 6-h paraxanthine to caffeine serum concentration ratio (0.49 +/- 0.3 before and 0.44 +/- 0.3 after, p > 0.05), were unchanged following clarithromycin dosing. Neither the tolbutamide oral clearance (0.77 +/- 0.28 l/h before and 0.72 +/-0.24 l/h after, p > 0.05) nor the tolbutamide urinary metabolic ratio (779 +/- 294 before and 681 +/- 416 after, p > 0.05) indices of CYP2C9 were altered by clarithromycin administration. In the case of CYP2D6, the dextromethorphan to dextrorphan urinary ratio was not significantly different before (0.021 +/- 0.04) and after (0.024 +/- 0.06) clarithromycin dosing. In conclusion, clarithromycin does not appear to alter the in vivo catalytic activity of CYP1A2, CYP2C9, and CYP2D6 in healthy individuals as assessed by caffeine, tolbutamide, and dextromethorphan, respectively.