A patient taking atorvastatin develops severe myopathy after adding gemfibrozil for hypertriglyceridemia. The pharmacokinetic basis of this interaction is:

• A Gemfibrozil induces CYP3A4, increasing atorvastatin metabolism to a toxic active metabolite
• B Gemfibrozil inhibits OATP1B1 (hepatic uptake transporter) and glucuronidation of statin lactone, increasing statin systemic exposure ✓
• C Gemfibrozil directly inhibits HMG-CoA reductase, doubling the pharmacodynamic effect
• D Both drugs compete for plasma protein binding, displacing statin into tissues

Explanation

Gemfibrozil inhibits the hepatic uptake transporter OATP1B1 (reducing hepatic statin uptake and first-pass elimination) and also inhibits glucuronidation of the statin lactone form; together these mechanisms markedly increase systemic statin exposure and skeletal muscle concentration, causing myopathy and potentially rhabdomyolysis. Fenofibrate has much weaker interaction with statins by this mechanism and is generally preferred over gemfibrozil when fibrate–statin combination is needed.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.