Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8.

Article Details

Citation

Tornio A, Pasanen MK, Laitila J, Neuvonen PJ, Backman JT

Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8.

Basic Clin Pharmacol Toxicol. 2005 Aug;97(2):104-8.

PubMed ID
15998357 [ View in PubMed
]
Abstract

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 microM) 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) muM, 8.4 (15) microM, 16 (38) microM and 19 (37) microM, respectively. Cerivastatin, simvastatin acid and lovastatin acid were less potent inhibitors with K(i) (IC(50)) values ranging from 32 to 55 (30--67) microM. Rosuvastatin and pravastatin showed no appreciable effect on CYP2C8 activity even at 100 microM. 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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
AtorvastatinCytochrome P450 2C8ProteinHumans
No
Substrate
Inhibitor
Details
LovastatinCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
SimvastatinCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Inhibitor
Details