An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins.
INTRODUCTION
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lower cholesterol synthesis in patients with hypercholesterolemia. Increased statin exposure is an important risk factor for skeletal muscle toxicity. Potent inhibitors of cytochrome P450 (CYP) 3A4 significantly increase plasma concentrations of the active forms of simvastatin, lovastatin, and atorvastatin. Fluvastatin is metabolized by CYP2C9, whereas pravastatin, rosuvastatin, and pitavastatin are unaffected by inhibition by either CYP. Statins also have different affinities for membrane transporters involved in processes such as intestinal absorption, hepatic absorption, biliary excretion, and renal excretion.


AREAS COVERED
In this review, the pharmacokinetic aspects of drug-drug interactions with statins and genetic polymorphisms of CYPs and drug transporters involved in the pharmacokinetics of statins are discussed.


EXPERT OPINION
Understanding the mechanisms underlying statin interactions can help minimize drug interactions and reduce the adverse side effects caused by statins. Since recent studies have shown the involvement of drug transporters such as OATP and BCRP as well as CYPs in statin pharmacokinetics, further clinical studies focusing on the drug transporters are necessary. The establishment of biomarkers based on novel mechanisms, such as the leakage of microRNAs into the peripheral blood associated with the muscle toxicity, is important for the early detection of statin side effects.
['Hirota|Takeshi|T|', 'Fujita|Yuito|Y|', 'Ieiri|Ichiro|I|']
D000818:Animals D002352:Carrier Proteins D003577:Cytochrome P-450 Enzyme System D004347:Drug Interactions D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D006937:Hypercholesterolemia D018482:Muscle, Skeletal D009135:Muscular Diseases D010597:Pharmacogenetics D011110:Polymorphism, Genetic
simvastatin Atorvastatin rosuvastatin genetic polymorphisms microRNA ABCG2 CYP3A4 SLCO1B1