説明
Cyclosporine inhibits OATP1B1/1B3 hepatic transporters and P-glycoprotein, substantially increasing pravastatin plasma concentrations and raising the risk of myopathy and rhabdomyolysis.
機序
Pravastatin is not metabolised by CYP enzymes but relies on OATP1B1-mediated hepatic uptake for its pharmacological effect and elimination; cyclosporine potently inhibits OATP1B1/1B3, trapping pravastatin in the systemic circulation.
臨床的意義
Pharmacokinetic studies show cyclosporine increases pravastatin AUC by approximately 10-fold; myopathy risk is significantly elevated despite pravastatin being considered lower risk than other statins.
対処法
Limit pravastatin dose to 20 mg/day in patients receiving cyclosporine; monitor for myopathy symptoms (muscle pain, weakness); measure CK if symptomatic.