A randomized cross-over pharmacokinetic study of rosuvastatin calcium (single dose: 5 mg, 10 mg and 20 mg; multiple doses: 10 mg once daily for 7 days) was conducted in 12 healthy Chinese volunteers. Plasma concentrations of rosuvastatin were determined by an LC-ESI-MS-MS method. Single-nucleotide polymorphisms (SNPs) in ABCB1, ABCG2, SLCO1B1, CYP2C9 and CYP3A5 were determined by TaqMan® (MGB) genotyping assay. An impact of the aforementioned SNPs on steady state pharmacokinetic parameters average steady state concentration (C av,ss) and area under the plasma concentration versus time curve during the dosing interval at steady state (AUC ss), dose-normalized (based on 5 mg) pharmacokinetic parameters of single-dose rosuvastatin were further analyzed. Rosuvastatin exhibited linear pharmacokinetics and great inter-subject variability. C av,ss, AUC ss and dose-normalized peak plasma concentration (C max) and AUC (0-∞) of single-dose rosuvastatin were significantly related with ABCB1 C1236T, G2677T/A and C3435T polymorphisms and ABCB1 haplotypes. Compared to homozygous wild type and heterozygous mutation gene carriers, subjects carrying the variant ABCB1 1236TT, 2677 non-G or 3435TT genotype had higher C av,ss, AUC ss, C max and AUC (0-∞) (p A had a significant impact on rosuvastatin pharmacokinetics. Homozygotes (AA) carriers had obvious higher C max (12.20 ± 4.09 μg·L–1 vs 8.70 ± 3.09 μg·L–1, p G, ABCG2 c.34G > A, SLCO1B1 c.521 T > C, c.388 A > G, g.11187 G > A, c.571 T > C and c.597 C > T. In addition, no difference in rosuvastatin pharmacokinetics was observed among subjects of different genders. We conclude that ABCB1 C1236T, G2677T/A and C3435T polymorphism, ABCB1 haplotypes and ABCG2 c.421C > A are determinants of inter-subject variability in rosuvastatin pharmacokinetics in healthy Chinese volunteers, and potentially affect the efficacy and toxicity of statin therapy.
Zhou et al. (Fri,) studied this question.