title: Drug-drug interactions that interfere with statin metabolism.
abstract: BACKGROUND
  Lipid-lowering drugs, especially hydroxymethylglutaryl-CoA reductase inhibitors (statins), are widely used in the treatment and prevention of atherosclerotic diseases. The benefits of statins are well documented. However, myotoxic side effects, which can sometimes be severe, including myopathy or rhabdomyolysis, have been associated with the use of statins. In some cases, this toxicity is associated with pharmacokinetic alterations. Potent inhibitors of CYP 3A4 significantly increase plasma concentrations of the active forms of simvastatin, lovastatin and atorvastatin. Fluvastatin is metabolized by CYP2C9, while pravastatin, rosuvastatin and pitavastatin are not susceptible to inhibition by any CYP.
  
  
  METHODS
  This review discusses the pharmacokinetic aspects of the drug-drug interaction with statins and genetic polymorphisms in CYPs, which are involved in the metabolism of statins, and highlights the importance of establishing a system utilizing electronic medical information practically to avoid adverse drug reactions.
  
  
  CONCLUSIONS
  An understanding of the mechanisms underlying statin interactions will help to minimize drug interactions and develop statins that are less prone to adverse interactions. Quantitatively analyzed information for the low-density lipoprotein cholesterol lowering effects of statin based on electronic medical records may be useful for avoiding the adverse effect of statins.
authors.affiliation: a Kyushu University, Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Department of Clinical Pharmacokinetics , Fukuoka 8128582, Japan +81 92 642 6657 ; +81 92 642 6660 ; ieiri-ttr@umin.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirota
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ieiri
mesh_terms: D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D050197:Atherosclerosis / Q000188:drug therapy; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D009135:Muscular Diseases / Q000139:chemically induced; D011110:Polymorphism, Genetic; D012206:Rhabdomyolysis / Q000139:chemically induced
chemical_list: D000924:Anticholesteremic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003577:Cytochrome P-450 Enzyme System
keywords: CYP2C9; CYP3A4; atorvastatin; electric medical record; fluvastatin; lovastatin; simvastatin