Cerivastatin metabolism

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. 

For instance/ the interaction between cerivastatin and gemfibrozil/ which has resulted in cases of severe rhabdomyolysiS/ is likely due to the inhibition of cerivastatin metabolism by gemfibrozil (i.e./ pharmacokinetic interaction)/ in addition to the propensity of both drugs to cause skeletal muscle toxicity (i.e./ pharmacodynamic interaction) (13-15). 

Fluvastatin may increase warfarin toxicity because both compete with P450 2C9 for metabolism. Cerivastatin can cause fatal rhabdomyolysis risk with other statins unclear. 

Cerivastatin uses a secondary CYP2C8-mediated metabolic pathway, which is unaffected by itraconazole (12). The effects of itraconazole on the pharmacokinetics of cerivastatin and its major metabolites have been investigated in a randomized, double-blind, crossover study (13). Inhibition of the CYP3A4-mediated M-l pathway led to raised serum concentrations of cerivastatin, cerivastatin lactone, and metabolite M-23, resulting in increased concentrations of active HMG-CoA reductase inhibitors. However, the effect was modest. 

T, Cheesman MJ, Kwok PY, Marciante K, Heckbert SR, Psaty BM, Totah RA (2010) Cerivastatin in vitro metabolism by CYP2C8 variants found in patients experiencing rhabdomyolysis. Pharmacogenet Genomics 20 619-629... 

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],... 

Shitara. Y.. Hirano. M.. Adachi. Y.. Itoh. T, Sato, H.. and Sugiyama. Y. (2004) fn vitro and in vivo correlation of the inhibitory effect of cyclosporin A on the transporter-mediated hepatic uptake of cerivastatin in rats. Drug Metabolism and Disposition, 32. 1468-1475. 

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