目的 分析高胆固醇血症患者阿托伐他汀血药浓度，建立阿托伐他汀的群体药动学模型，考察SLCO1B1基因多态的影响。方法 选取2023年1月—2024年6月六安市人民医院收治的高胆固醇血症患者作为研究对象，口服阿托伐他汀钙片，起始剂量20 mg，1次/d。采用HPLC-MS/MS法测定阿托伐他汀血药浓度。采用多态性聚合酶链式反应（PCR）法鉴定SLCO1B1基因c.521T＞C位点多态性。构建群体药动学模型，计算患者阿托伐他汀清除率，分析其与患者随访期间肌酸激酶均值和低密度脂蛋白差值的相关性。结果 136例患者的阿托伐他汀血药浓度谷浓度0.29～2.12 ng/mL，峰浓度1.12～12.27 ng/mL。基因频率分布具有较好的群体代表性。阿托伐他汀表观清除率与肌酸激酶、低密度脂蛋白差值呈明显负相关。结论 SLCO1B1基因c.521T＞C位点多态性是影响阿托伐他汀清除的重要因素，其与患者降脂效果和用药安全性风险密切相关。

Objective To analyze the atorvastatin blood concentration in patients with hypercholesterolemia, establish a population pharmacokinetic model for atorvastatin, and investigate the influence of SLCO1B1 gene polymorphism. Methods Patients with hypercholesterolemia admitted to Lu’an People's Hospital from January 2023 to June 2024 were selected as the study subjects. They were po administered with Atorvastatin Calcium Tablets at an initial dose of 20 mg, once daily. The blood concentration of atorvastatin was determined by HPLC-MS/MS method. The c.521T > C polymorphism of the SLCO1B1 gene was identified using PCR method. A population pharmacokinetic model was constructed to calculate the atorvastatin clearance rate for patients and analyzed its correlation with the mean creatine kinase levels and the difference in low-density lipoprotein during follow-up. Results The trough concentration range of atorvastatin in 136 patients was 0.29 — 2.12 ng/mL, and the peak concentration range was 1.12 — 12.27 ng/mL. The gene frequency distribution had good population representativeness. The apparent clearance rate of atorvastatin was significantly negatively correlated with the difference in creatine kinase and low-density lipoprotein difference. Conclusion The c.521T > C polymorphism of SLCO1B1 gene is an important factor affecting the clearance of atorvastatin, which is closely related to the lipid-lowering effect and medication safety risk in patients.

R968;R973

国家自然科学基金资助项目（82300841）；安徽省高校自然科学研究项目（KJ2021A0342）；安徽医科大学校科研基金项目（2020xkj231）；六安市科技计划项目（2022lakj013）