Population Pharmacokinetics Research of Simvastatin in Elderly Patients with Hyperlipidemia
Hao Wang · Zhongguo yaofang · 2012
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.