Pharmacokinetics of Rosuvastatin: A Systematic Review of Randomised Controlled Trials in Healthy Adults

Abstract

Background: Rosuvastatin is a lipid-lowering drug that works by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme responsible for producing cholesterol in humans. The pharmacokinetic data of rosuvastatin are considerably variable across studies.

Objective: To review the pharmacokinetics of rosuvastatin from randomised controlled trials (RCTs) in healthy adults.

Methods: A review of the pharmacokinetics of rosuvastatin was performed using systematic search strategies. The Sheiner method was used to summarise the pharmacokinetics of the drug.

Results: Randomised controlled studies (n = 70) involving healthy subjects (n = 2355) that examined the pharmacokinetics of rosuvastatin following single and multiple doses were included in the review. Rosuvastatin is given once daily in the dose range of 5-80 mg, with 40 mg being the maximum approved daily dose. Rosuvastatin achieves maximum plasma concentration at a median of 5 h (range: 0.5-6 h) under fasting conditions following single and multiple doses. Following single doses, rosuvastatin has a mean absolute oral availability of 20%, an overall mean total clearance of 28.3 L/h and an average terminal elimination half-life of approximately 20 h. The overall mean total clearance of the drug in Caucasian subjects was 1.7-fold higher than that in healthy Chinese subjects. The systemic exposure of rosuvastatin is characterised by a large coefficient of variation (48%.) There is a small accumulation with repeated dosing. The interaction of rosuvastatin with darunavir/ritonavir was considered statistically and clinically relevant. Interactions of rosuvastatin single doses with erythromycin, fluconazole, itraconazole and antacid were statistically significant.

Discussion and conclusions: There is considerable variation in the pharmacokinetics of rosuvastatin between races. The clinical relevance of the statistically significant drug interactions is yet to be investigated following repeated co-administration for at least 15 days, consistent with a half-life of low-density lipoprotein of 3 days.