Food Effect on Rosuvastatin Disposition and Low-Density Lipoprotein Cholesterol

Rosuvastatin is commonly prescribed for the treatment of hypercholesterolemia and hepatic transporter-mediated accumulation in the liver enhances its efficacy. Current guidelines indicate no preference for fed or fasted rosuvastatin administration. We investigated the association between food intake and rosuvastatin disposition in healthy subjects and low-density lipoprotein cholesterol (LDL-C)-lowering effects among patients taking rosuvastatin. We demonstrate that administration with food resulted in a near 40% reduction of rosuvastatin exposure in healthy Asian (n = 12) and Caucasian (n = 11) subjects. Higher rosuvastatin concentrations in Asian subjects also correlated with higher allele frequency of ABCG2 c.421C>A. In mice, a greater rosuvastatin liver:plasma ratio was noted when administered with food. Among rosuvastatin patients (n = 156), there was no difference in dose needed to reach target LDL-C, measured LDL-C, or lathosterol concentrations, when administered in a fed or fasting state. Therefore, taking rosuvastatin with food could reduce systemic concentrations, and subsequent myopathy risk, without compromising LDL-C-lowering benefit.