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目的观察辛伐他汀在稳定血液透析患者的药物代谢动力学特征,以及可能的影响因素。方法稳定血液透析患者一次性服用辛伐他汀20 mg,用药后不同时间采血,用HPLC-MS/MS测定辛伐他汀血药浓度,以非线性混合效应模型法(NONMEM)进行分析,得到群体药代动力学参数,并与文献中正常人辛伐他汀药代动力学参数进行比较。结果共23例患者参加该研究,获得95份血样,平均年龄60.48岁。最终模型的药代动力学参数估计值(95%可信区间)分别为,CL1为663(375～951)L.h-1;CL2为197(42.7～351)L.h-1,V1为119(32.2～206)L;V2为1830(905～2760)L;Ka为0.59(0.37～0.82)h-1;Tlag为0.49(0.48～0.50)h。血液透析器(滤器)、吸烟、体重指数可能影响药物的清除率。推算患者的药代动力学参数,t1/2为(6.83±10.79)h;Cmax为(12.25±8.35)μg·L-1;tmax为(0.90±0.27)h;AUC0→t为(30.80±25.00)μg·h.L-1。结论本研究所得群体药代动力学模型可能实现血透患者辛伐他汀个体化药物调整。
Objective To observe the pharmacokinetic characteristics of simvastatin in stable hemodialysis patients and its possible influencing factors. Methods One-time simvastatin 20 mg was given to patients with stable hemodialysis. Blood samples were drawn at different times after administration. The plasma concentration of simvastatin was determined by HPLC-MS / MS and analyzed by non-linear mixed-effects model (NONMEM) The pharmacokinetic parameters were compared with the simvastatin pharmacokinetic parameters in the literature. Results A total of 23 patients participated in the study, obtaining 95 blood samples with an average age of 60.48 years. The estimated pharmacokinetic parameters of the final model (95% confidence interval) were CL3 663 (375-951) Lh-1, CL2 197 (42.7-351) Lh-1 and V1 119 206) L; V2 is 1830 (905-2760) L; Ka is 0.59 (0.37-0.82) h-1; Tlag is 0.49 (0.48-0.50) h. Hemodialyzer (filter), smoking, body mass index may affect drug clearance. The pharmacokinetic parameters of patients were calculated, t1 / 2 was (6.83 ± 10.79) h, Cmax was (12.25 ± 8.35) μg · L-1, tmax was (0.90 ± 0.27) h, AUC0 → t was (30.80 ± 25.00) ) μg · hL-1. Conclusion The population pharmacokinetic model obtained in this study may be able to achieve individualized adjustment of simvastatin in hemodialysis patients.