辛伐他汀在老年高血脂患者中的群体药动学研究

目的：考察老年高血脂患者口服辛伐他汀的药动学模型,为临床制订个体化给药方案提供参考。方法：以30例服用辛伐他汀降血脂的老年高血脂患者为研究对象,于服药前与服药后20、62d3个时间点采血,以高效液相色谱（HPLC）法测定血药浓度,以生化法测定肌酐（Cr）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）等实验室检查指标;运用非线性混合效应模型（NONMEM）建立辛伐他汀的药动学模型;考察年龄、体重、肌酐清除率（CLcr）、ALT和AST等对药动学参数的影响,并以Bootstrap法进行模型验证。结果：本研究建立了口服辛伐他汀一级吸收和消除的一房室群体药动学模型;年龄、体重、CLcr等因素加入模型之后,基本模型并未改变（P〉0.05）。辛伐他汀表观清除率和表观分布容积的群体典型值分别为1020L·h-1和2350L。结论：本研究建立了老年高血脂患者口服辛伐他汀的群体药动学模型,为临床合理使用该药提供了依据。

Population Pharmacokinetics Research of Simvastatin in Elderly Patients with Hyperlipidemia

OBJECTIVE： To explore the pharmacokinetics （PK） model of oral simvastatin in elderly patients with hyperlipidemia and provide reference for individualized medication scheme in clinical practice. METHODS： 30 elderly patients with hyperlipidemia, who were orally administered with simvastatin, were enrolled in this study. Blood samples were collected before medication, and 20 days and 62 days after medication. The plasma concentration was determined by HPLC. The laboratory parameters, such as Cr, ALT, AST, and so on, were determined by biochemical method. Nonlinear mixed effect modeling （NONMEM） was employed to establish the PK model of simvastatin. The effects of age, body weight, CLcr, ALT, AST on parameters of PK were estimated. The final PK model was validated by Bootstrap method. RESULTS： A one-compartment model with first-order absorption and elimination was built. The model, which fixed effects were added into, did not improve the basic model（P0.05）. The typical population values of apparent clearance and apparent volume were： 1 020 L·h-1 and 2 350 L respectively. CONCLUSION： The PK model of oral simvastatin in elderly patients with hyperlipidemia has been established in the study, to provide reference for rational use of simvastatin in the clinic.