Gemfibrozil CYP2C8 inhibition

The British National Formulary (BNF) recommends that fibrates or nicotinic acid should not be combined with statins because of the potential for myopathy and rhabdomyolysis with this combination [54]. This is widely discussed in the medical literature. Numerous deaths have been reported and the high mortality associated with concurrent use of cerivastatin and gemfibrozil was partly instrumental in the decision to withdraw cerivastatin from the market in 2001 [34]. It appears that the high mortality in patients using concurrent gemfibrozil and cerivastatin was due to interactions at the level of glucuronidation, CYP2C8 inhibition and OATP inhibition [17, 55]. 

Wang JS, Neuvonen M, Wen X, et al. Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. Drug Metab Dispos 2002 30 1352-1356. 

Gemfibrozil increased the plasma concentration of cerivastatin, mainly caused by the inhibition of CYP2C8-mediated metabolism of cerivastatin by gemfibrozil glucuronide, which may be concentrated in hepatocytes, and partly caused by its inhibition of OATP1 Bl-mediated uptake [207, 215],... 

OATPIBI (SLCO) Gemfibrozil Cerivastatin > 5-fold increase in AUC Inhibition of hepatic sinusoidal OATPIBI also inhibition of MRP2 BCRP CYP2C8... 

Filppula AM, Tornio A, Niemi M, Neuvonen PJ, Backman JT (2013) Gemfibrozil impairs imatinib absorption and inhibits the CYP2C8-mediated formation of its main metabolite. Clin Pharmacol Ther 94 383-393... 

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