【摘要】 目的 :建立中国癫痫病患者丙戊酸清除率的群体药动学模型。方法 :前瞻性收集上海、北京两地 4所医院服用丙戊酸的 35 0名患者的稳态血药浓度 (n =4 35 )。数据分析采用非线性混合效应模型。结果 :最终模型为 :CL(L·h-1) =0 .0 4 2 2·Dose·BSA0 .2 69·1.4 1(如果合用卡马西平 ,否则为 1)·1.37(如果合用苯妥因 ,否则为 1)·(0 .0 0 735·PBS +0 .80 7) (如果合用苯巴比妥 ,否则为 1)·(Dose/ 95 0 ) (如果Dose大于 95 0mg·m-2 ·d-1,否则为 1)·1.2 1(如果BSA大于 1.7m2 ,否则为 1)·1.2 4 (如果年龄小于 6 ,否则为 1)。上式中Dose为日剂量 (mg·m-2 ·d-1) ;BSA为体表面积 (m2 ) ;PBS为苯巴比妥的日剂量 (mg·m-2 ·d-1)。结论 :根据患者的生理用药资料 ,结合上述模型 ,可估算其清除率 ,为制定给药方案提供依据。更多还原

【Abstract】 OBJECTIVE To establish a clearance model for valproic acid by population pharmacokinetic method. METHODS Steady state serum concentration data （n=435） were collected from 350 epilepsy patients in Shanghai and Beijing during their routine clinical care. Nonlinear mixed effect model was employed to establish the population pharmacokinetic model of the valproic acid clearance （CL）. RESULTS The final model was: CL（L·h_-1）=₀.0422·Dose·BSA₀.269·₁.41（if taking carbamazepine,otherwise it equals to 1）·₁.37 （if taking phenytoin,otherwise it equals to 1）·（₀.00735·PBS+₀.807）（if taking Phenobarbital,otherwise it equals to 1）·（dose/950）（if dose greater than 950 mg·m_-2·d_-1, otherwise it equals to 1）·₁.21 （if BSA greater than ₁.7 m2, otherwise it equals to 1）·₁.24 （if patients less than 6 years old,otherwise it equals to 1）in which dose is daily dose （mg·m_-2·d_-1）, BSA is body surface area （m2） and PBS is daily phenobarbital dose （mg·m_-2·d_-1）.CONCLUSION A population pharmacokinetic model is proposed to estimate the individual CL for patients taking valproic acid in terms of patients’ characteristics and dosing history, and to establish a prior dosage regimen.更多还原