TY - JOUR T1 - In Vivo Effect of Clarithromycin on Multiple Cytochrome P450s JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1023 LP - 1028 VL - 29 IS - 7 AU - Melissa A. Bruce AU - Stephen D. Hall AU - Barbara D. Haehner-Daniels AU - J. Christopher Gorski Y1 - 2001/07/01 UR - http://dmd.aspetjournals.org/content/29/7/1023.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -