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Mibefradil, a potent CYP3A inhibitor, does not alter pravastatin pharmacokinetics
Author(s) -
Becquemont Laurent,
FunckBrentano Christian,
Jaillon Patrice
Publication year - 1999
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1999.tb00344.x
Subject(s) - mibefradil , pravastatin , pharmacokinetics , pharmacology , cyp3a , chemistry , medicine , endocrinology , cytochrome p450 , cholesterol , antagonist , metabolism , receptor
— 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 CYP3A 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 mibefradil (day 1) and after repeated doses (100 mg/day) of mibefradil (day 8). Pravastatin pharmacokinetics after repeated doses of 40 mg/day was also studied in association with repeated doses (100 mg/day) of mibefradil (day 16). Pravastatin area under the plasma concentration vs. time curve (AUC 0‐∞ ,) and C max in the absence of mibefradil on day 1 (170 [117 to 395] ng h/mL and 91 [72 to 200] ng/mL respectively, geometric mean [95% confidence 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 slightly delayed in the presence of mibefradil on day 8 and 16 (1.1 ± 0.3 and 1.2 ± 0.3 h respectively, p < 0.01 for both comparisons). The results of the present study confirm the lack of pharmacokinetic interactions between mibefradil and pravastatin and indicate that pravastatin may be safely prescribed in the presence of potent CYP3A inhibitors.