Pharmazie
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Randomized Controlled Trial
ABCB1 gene polymorphisms, ABCB1 haplotypes and ABCG2 c.421c > A are determinants of inter-subject variability in rosuvastatin pharmacokinetics.
A randomized cross-over pharmacokinetic study of rosuvastatin calcium (single dose: 5 mg, 10 mg and 20 mg; multiple doses: 10mg 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, SLCOB1, CYP2C9 and CYP3A5 were determined by TaqMan (MGB) genotyping assay. ⋯ There were no significant effects on single-dose and steady-state pharmacokinetics of rosuvastatin by CYP2C9*3 (1075A > C), CYP3A5*3 g.6986A > 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.
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A pharmacokinetic study of simvastatin (single oral dose, 40 mg) was conducted in 17 healthy Chinese volunteers. Plasma concentrations of simvastatin were determined by an LC-ESI-MS-MS method. The pharmacokinetic parameters of simvastatin were derived with a non-compartmental method. ⋯ We conclude here that there is a small inter-subject variation in simvastatin pharmacokinetics in healthy Chinese volunteers. P-gp, OATP1 B1 and BCRP seem unlikely to play an important role in the pharmacokinetics of simvastatin. The gene-dose effects of ABCG2 c.421 C > A and CYP3A5*3 g.6986A > G on simvastatin pharmacokinetics are not strong enough in Chinese subjects.