Clinical and Pharmacogenetic Predictors of Circulating Atorvastatin and Rosuvastatin Concentrations in Routine Clinical Care

Abstract

Background—A barrier to statin therapy is myopathy associated with elevated systemic drug exposure. Our objective was to examine the association between clinical and pharmacogenetic variables and statin concentrations in patients. Methods and Results—In total, 299 patients taking atorvastatin or rosuvastatin were prospectively recruited at an outpatient referral center. The contribution of clinical variables and transporter gene polymorphisms to statin concentration was assessed using multiple linear regression. We observed 45-fold variation in statin concentration among patients taking the same dose. After adjustment for sex, age, body mass index, ethnicity, dose, and time from last dose, SLCO1B1 c.521T>C (PA (PG (PC (P<0.05) and 4β-hydroxycholesterol, a CYP3A activity marker (adjusted R2=0.47). A second cohort...