Wang Chang-Lian, Lin Wei-Wei, Gong Shi-Ju, Huang Pin-Fang
Department ofPharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
Yao Xue Xue Bao. 2010 Nov;45(11):1427-32.
The paper is to report the establishment of a population pharmacokinetic model for flurbiprofen (FP), an active metabolite of flurbiprofen axetil (FA). 246 FP serum concentration and clinical data were perspectively collected from 23 general anaesthesia patients receiving FA intravenously before operation in Dentofacial Surgery and Otorhinolaryngology Department of the First Affiliated Hospital of Fujian Medical University. Population pharmacokinetic data analysis was performed using NONMEM software. The measure of Bootstrap was applied for internal validation, while Visual Predictive check was adopted for external validation. The data of FP correspond with two-compartment model. The body weight (WT) had conspicuous effect on clearance and volume of central compartment, while sex, age and daily dose of administration had no marked effect on pharmacokinetic parameter of FP. The basic model was described as follows: CL (L x h(-1)) = 1.28x EXP(ETA(1)), V1 (L) = 5.03x EXP(ETA(2)), Q (L x h(-1)) = 8.5 x EXP(ETA(3)), V2 (L) = 4.39 x EXP(ETA(4)). The final model was described as follows: CL (L x h(-1)) = 1.32 x (WT/60) x EXP(ETA(1)), V1 (L) = 5.23 x (WT/60) x EXP(ETA(2)), Q (L x h(-1)) = 8.45 x EXP(ETA(3)), V2 (L) = 4.37 x EXP(ETA(4)). The population typical value of CL, V1, Q and V2 were: 1.32 L x h(-1), 5.23 L, 8.45 L x h(-1) and 4.37 L, respectively. Bootstrap and visual predictive check show that the final model of FP is stable, effective and predictable. A novel population pharmacokinetic model is developed to estimate the individual pharmacokinetic parameter for patients intravenous injecting FA in terms of patients' characteristics and dosing history, and to design a prior dosage regimen.
本文旨在报道氟比洛芬酯（FA）的活性代谢产物氟比洛芬（FP）群体药代动力学模型的建立。前瞻性收集福建医科大学附属第一医院口腔颌面外科及耳鼻咽喉科23例手术前接受FA静脉注射的全身麻醉患者的246份FP血清浓度及临床资料。使用NONMEM软件进行群体药代动力学数据分析。采用Bootstrap法进行内部验证，采用可视化预测检验进行外部验证。FP的数据符合二室模型。体重（WT）对清除率和中央室容积有显著影响，而性别、年龄和每日给药剂量对FP的药代动力学参数无明显影响。基本模型如下：CL（L×h⁻¹）=1.28×EXP(ETA(1))，V1（L）=5.03×EXP(ETA(2))，Q（L×h⁻¹）=8.5×EXP(ETA(3))，V2（L）=4.39×EXP(ETA(4))。最终模型如下：CL（L×h⁻¹）=1.32×(WT/60)×EXP(ETA(1))，V1（L）=5.23×(WT/60)×EXP(ETA(2))，Q（L×h⁻¹）=8.45×EXP(ETA(3))，V2（L）=4.37×EXP(ETA(4))。CL、V1、Q和V2的群体典型值分别为：1.32 L×h⁻¹、5.23 L、8.45 L×h⁻¹和4.37 L。Bootstrap法和可视化预测检验表明，FP的最终模型稳定、有效且具有可预测性。建立了一种新的群体药代动力学模型，根据患者的特征和给药史估算静脉注射FA患者的个体药代动力学参数，并设计先验给药方案。
