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Comparison of 3‐Hydroxy‐3‐methylglutaryl Coenzyme A (HMG‐CoA) Reductase Inhibitors (Statins) as Inhibitors of Cytochrome P450 2C8
Author(s) -
Tornio Aleksi,
Pasanen Marja K.,
Laitila Jouko,
Neuvonen Pertti J.,
Backman Janne T.
Publication year - 2005
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2005.pto_134.x
Subject(s) - cerivastatin , pravastatin , fluvastatin , rosuvastatin , pharmacology , lovastatin , simvastatin , cyp2c8 , atorvastatin , chemistry , hmg coa reductase , pitavastatin , statin , reductase , gemfibrozil , cytochrome p450 , cyp2c9 , biochemistry , cholesterol , medicine , enzyme
Statins are involved in different types of drug interactions. Our objective was to study the effect of statins on cytochrome P450 (CYP) 2C8‐mediated paclitaxel 6α‐hydroxylation by incubating paclitaxel and statins (0–100 μM) with pooled human liver microsomes. Simvastatin, lovastatin, atorvastatin and fluvastatin were the most potent inhibitors of CYP2C8 activity with K i (IC 50 ) values of 7.1 (9.6) μM, 8.4 (15) μM, 16 (38) μM and 19 (37) μM, respectively. Cerivastatin, simvastatin acid and lovastatin acid were less potent inhibitors with K i (IC 50 ) values ranging from 32 to 55 (30–67) μM. Rosuvastatin and pravastatin showed no appreciable effect on CYP2C8 activity even at 100 μM. In conclusion, all the statins tested, except rosuvastatin and pravastatin, had a significant inhibitory effect on the activity of CYP2C8 in vitro. Because many of the statins accumulate in the liver and because also their metabolites may inhibit CYP2C8 activity, in vivo studies are needed to investigate a possible interaction of simvastatin, lovastatin, atorvastatin and fluvastatin with CYP2C8 substrate drugs.