Impacts of Pharmacokinetic Gene Polymorphisms on Steady‐State Plasma Concentrations of Simvastatin in Thai Population

作者：Sayanit Tipnoppanon, Udomsak Udomnilobol, Sarawut Siwamogsatham, Yongkasem Vorasettakarnkij, Chonlaphat Sukasem, Thomayant Prueksaritanont, Pajaree Chariyavilaskul, Varalee Yodsurang, Thanate Srimatimanon, Monpat Chamnanphon, Natchaya Vanwong · 发表于：Clinical and Translational Science · 年份：2025 · DOI：10.1111/cts.70225 · 被引用次数：3 · 研究领域：Lipoproteins and Cardiovascular Health、Drug Transport and Resistance Mechanisms、Computational Drug Discovery Methods

Simvastatin, an HMG-CoA reductase inhibitor, is widely used for hypercholesterolemia but may cause myotoxicity linked to its plasma concentration. Pharmacokinetic gene polymorphisms influence inter-individual variability in simvastatin exposure. This study investigated the effects of pharmacokinetic gene polymorphisms on steady-state simvastatin plasma levels in Thai patients. Eighty-nine Thai patients with dyslipidemia or coronary artery disease on simvastatin treatment for at least 2 weeks without dose adjustment were recruited from King Chulalongkorn Memorial Hospital. Simvastatin lactone and acid concentrations were measured 12 h post-dose using UHPLC-MS/MS. Pharmacokinetic gene polymorphisms, including ABCB1, ABCC2, ABCG2, SLCO1B1, SLCO1B3, CYP3A4, and CYP3A5, were genotyped by MassARRAY System. The results showed that patients with the SLCO1B1 c.521TC+CC genotype had significantly higher simvastatin acid levels than those with c.521TT (0.53 vs. 0.19 ng/mL, p = 0.03). Similarly, the SLCO1B1*1b/*15 genotype was associated with higher simvastatin acid levels than SLCO1B1*1a/*1a (0.58 vs. 0.16 ng/mL, p < 0.001). These findings suggest that SLCO1B1 c.521T>C, alone or with c.388A>G (SLCO1B1*1b/*15), reduces OATP1B1 function, leading to elevated simvastatin acid levels and increased myotoxicity risk. This study confirms the association of SLCO1B1 rs4149056 (c.521T>C) with higher simvastatin plasma levels in Thai patients. The study highlights the potential role of SLCO1B1 geno...