Mibefradil, a potent CYP3A inhibitor, does not alter pravastatin pharmacokinetics

Dramatic drug-drug interactions have been observed between several HMG-CoA reductase inhibitors and cytochrome P450 3A (CYP3A) inhibitors. The aim of the present study was to investigate the effects of mibefradil, a potent CY P3A inhibitor, on pravastatin pharmacokinetics. 12 healthy volunteers were included in this open-label one-period study. Pravastatin pharmacokinetics (following a single oral dose of 40 mg) was studied in the absence of mibef radil (day 1) and after repeated doses (100 mg/day) of mibefradil (day 8). Pravastatin pharmacokinetics after repeated doses of 40 mg/day was also stu died in association with repeated doses (100 mg/day) of mibefradil (day 16) . Pravastatin area under the plasma concentration vs. time curve (AUC(0-inf inity)) and C-max in the absence of mibefradil on day 1 (170 [117 to 395] n g h/mL and 91 [72 to 200] ng/mL respectively, geometric mean [95% confidenc e intervals]) were not significantly altered in the presence of mibefradil on day 8 (224 [174 to 381] ng h/mL and 124 [72 to 200] ng/mL) and on day 16 (200 [137 to 555] ng h/mL and 91 [74 to 184] ng/mL). T-max of pravastatin in the absence of mibefradil (0.9 +/- 0.1 h, arithmetic mean +/- SD) was sl ightly delayed in the presence of mibefradil on day 8 and 16 (1.1 +/- 0.3 a nd 1.2 +/- 0.3 h respectively, p < 0.01 for both comparisons). The results of the present study confirm the lack of pharmacokinetic interactions betwe en mibefradil and pravastatin and indicate that pravastatin may be safely p rescribed in the presence of potent CYP3A inhibitors. (C) Elsevier, Paris.