A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P4502C8
Tekijät: Tornio A, Pasanen MK, Laitila J, Neuvonen P, Backman JT
Kustantaja: WILEY
Julkaisuvuosi: 2005
Journal: Basic and Clinical Pharmacology and Toxicology
Tietokannassa oleva lehden nimi: BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
Lehden akronyymi: BASIC CLIN PHARMACOL
Vuosikerta: 97
Numero: 2
Aloitussivu: 104
Lopetussivu: 108
Sivujen määrä: 5
ISSN: 1742-7835
DOI: https://doi.org/10.1111/j.1742-7843.2005.pto_134.x
Tiivistelmä
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 6 alpha-hydroxylation by incubating paclitaxel and statins (0-100 mu M) with pooled human liver microsomes. Simivastatin, lovastatin, atorvastatin and fluvastatin were the most potent inhibitors of CYP2C8 activity with K-i (IC50) values of 7.1 (9.6) mu M, 8.4 (15) mu M, 16 (38) mu M and 19 (37) mu M, respectively. Cerivastatin, simvastatin acid and lovastatin acid were less potent inhibitors with Ki (IC50) values ranging from 32 to 55 (30-67) mu M. Rosuvastatin and pravastatin showed no appreciable effect on CYP2C8 activity even at 100 mu M. 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.
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 6 alpha-hydroxylation by incubating paclitaxel and statins (0-100 mu M) with pooled human liver microsomes. Simivastatin, lovastatin, atorvastatin and fluvastatin were the most potent inhibitors of CYP2C8 activity with K-i (IC50) values of 7.1 (9.6) mu M, 8.4 (15) mu M, 16 (38) mu M and 19 (37) mu M, respectively. Cerivastatin, simvastatin acid and lovastatin acid were less potent inhibitors with Ki (IC50) values ranging from 32 to 55 (30-67) mu M. Rosuvastatin and pravastatin showed no appreciable effect on CYP2C8 activity even at 100 mu M. 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.
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