Читать книгу Transporters and Drug-Metabolizing Enzymes in Drug Toxicity - Albert P. Li - Страница 56

Cerivastatin is one of the drugs where toxicity can be a function of both drug metabolism and transport. Besides being a CYP2C8 inhibitor, Gemfibrozil and its glucuronide are inhibitors of cerivastatin uptake by the organic anion transporting polypeptide 2 (OATP2/OATP1B1:SLC21A6) [58, 63]. Inhibition of transporter‐mediated uptake of cerivastatin into hepatocytes leads to lower hepatic metabolic clearance. Physiologically based pharmacokinetic (PBPK) models have been developed to evaluate the complex interaction between cerivastatin and gemfibrozil, taking into account the inhibitory effects of gemfibrozil on cerivastatin uptake and metabolism [64, 65].