Population pharmacokinetics of rosuvastatin: implications of renal impairment, race, and dyslipidaemia.

ABSTRACTObjectives: To build the structural model of pharmacokinetics for rosuvastatin and evaluate the impact of demographic characteristics including renal function on its pharmacokinetic parameters.Methods: A population pharmacokinetic analysis of rosuvastatin in healthy volunteers, subjects with dyslipidaemia, and renal failure patients was performed using non-linear mixed-effects modelling and a two-compartment pharmacokinetic model with simultaneous first- and zero-order absorption. Demographic covariates, dyslipidaemic state and renal function were evaluated for their impact on pharmacokinetic parameters by step-wise additions or deletions using the likelihood ratio test.Results: Typical pharmacokinetic parameters were estimated for a healthy white male subject. For example, apparent oral clearance (CL/F ) was estimated to be 257 L/h. Age, smoking status, weight, body surface area, and lean body mass had no significant effect on rosuvastatin pharmacokinetics. The model predicted that CL/F for subje...