Population pharmacokinetic modeling of flurbiprofen

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·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)).  The final model was described as follows: 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)).  The population typical value of CL, V₁, Q and V₂ were: 1.32 L·h⁻¹, 5.23 L, 8.45 L·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.