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Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro *
Author(s) -
Mc Donnell C. G.,
Shorten G.,
Van Pelt F. N. A. M.
Publication year - 2005
Publication title -
anaesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.839
H-Index - 117
eISSN - 1365-2044
pISSN - 0003-2409
DOI - 10.1111/j.1365-2044.2005.04110.x
Subject(s) - fluvastatin , atorvastatin , cyp3a4 , midazolam , microsome , pharmacology , cytochrome p450 , in vitro , medicine , metabolism , non competitive inhibition , endocrinology , enzyme , chemistry , biochemistry , simvastatin , sedation
Summary We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)‐mediated metabolism of midazolam in vitro , using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis–Menten constant (K m ) of 5.25 (SD 1.2) μmol.l −1 . Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (K i ) of 12.4 (95% CI 4.65–20.06) μmol.l −1 . Fluvastatin was a weak non‐competitive inhibitor of CYP 3A4 with a K i of 94.3 (95% CI 55.01–133.5) μmol.l −1 . Both atorvastatin and fluvastatin inhibit the CYP 3A4‐mediated metabolism of midazolam in vitro .