Pharmacokinetic Properties of Rosuvastatin After Single-Dose, Oral Administration in Chinese Volunteers: A Randomized, Open-Label, Three-Way Crossover Study

Abstract Background: Rosuvastatin, a 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor (“statin”), has been marketed for the treatment of patients with dyslipidemia. Objectives: The objective of this study was to assess the dose proportionality and pharmacokinetic (PK) properties of rosuvastatin after single-dose administration in Chinese volunteers. The effects of food and sex on the PK properties of rosuvastatin in these volunteers were also assessed. Methods: This single-dose, randomized, open-label, 3-way crossover trial was conducted at West China Second University Hospital, Sichuan University, Chengdu, People's Republic of China. Healthy, male and female, adult (aged 20-24 years), Han Chinese volunteers were enrolled. Volunteers were allocated to receive, in randomized order according to a computer-generated randomization schedule, single doses of rosuvastatin (5, 10, and 20 mg) administered in separate trial periods, with a 1-week washout between periods. PK properties (Cmax , Tmax , AUC0-t , apparent elimination t1/2 ) and tolerability were assessed immediately before (0 hour) and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 15, 24, 36, 48, and 72 hours after study drug administration. The Student-Newman-Keuls test was used to test for linearity. The effects of food intake and sex on the PK properties of rosuvastatin were also investigated in subanalyses using standardized meals and the t test of logarithm-transformed (lg) values to detect differences in Cmax and AUC0-t between sexes and between the fed (test) and fasted (reference) states. All of the results were corrected for dose by weight (mg/kg). Results: The study enrolled 12 healthy Chinese volunteers (6 men: mean [SD] age, 22.3 [1.5] years; mean [SD] weight, 61.8 [2.4] kg [range, 59-64 kg]; 6 women: mean [SD] age, 21.6 [1.4] years; mean [SD] weight, 56.4 [6.4] kg [range, 50-64 kg]). Geometric mean (SD) Cmax values of 10.22 (8.05), 25.86 (18.77), and 44.99 (17.99) ng/mL were achieved at a median Tmax of 2.5 hours after administration of single doses of 5, 10, and 20 mg of rosuvastatin, respectively; the corresponding geometric mean (SD) values of AUC0-t were 73.67 (48.78), 210.21 (178.70), and 303.81 (193.29) ng/mL · h-1 , and the mean (SD) apparent elimination t1/2 values were 13.01 (8.68), 13.33 (5.21), and 15.40 (5.43) hours after administration. The Student-Newman-Keuls test results found that Cmax and AUC0-t were both linearly related to dose. In men, the mean (SD) Cmax values were 7.