The Population Pharmacokinetics Research Of Nifedipine Sustained-release/Controlled-release Preparation And Immediate-release Preparation In Healthy Volunteers

Objective: To investigate the population pharmacokinetics(PPK) characteristics of nifedipine sustained-release/controlled-release preparation and nifedipine immediate release preparation in healthy volunteers, providing a theoretical reference for the clinical optimization of nifedipine. Methods: Literatures about pharmacokinetics of nifedipine were retrieved from Wan fang medical database, VIP, CNKI, Pub Med and Medline database with the search words of nifedipine, pharmacokinetics and bioavailability, and the time was limited from January 2004 to December 2014.The blood concentration data of nifedipine in the literatures were gained by Get Data software, then the Nonlinear mixed effect modeling(NONMEM) was employed to establish the PPK model of Nifedipine sustained-release/controlled-release preparation and the PPK model of Nifedipine immediate-release preparation. The parameters of population pharmacokinetics and inter- and intra-individual variability had been investigated again. The final PPK model was validated and evaluated by Bootstrap method and visual predictive checking(VPC). Results:One-compartment model with first-order absorption and elimination was built in healthy volunteers. The population pharmacokinetic parameters were estimated as followed:(1) The typical population values of nifedipine sustained-release/controlled-release preparation of CL/F, V/F and Ka were 34.3L·h-1,1070 L and 0.125h-1, respectively. The inter-individual variability of these parameters were 82.8%, 42.5% and 60.8%, respectively.(2) The nifedipine immediate-release preparation of CL/F and V/F were 46L·h-1 and 117 L. The inter-individual variability of these parameters were 26.6%, 9.5%. Final model has been validated and evaluated by Bootstrap method and VPC method, which showing good stability and predictive efficacy.Conclusions: The population pharmacokinetic model of nifedipine sustained-release /controlled-release preparation and nifedipine immediate-release preparation in healthy volunteers were built, respectively. The typical population values, such as CL/F, V/F and Ka were 34.3L·h-1, 1070 L and 0.125h-1 in nifedipine sustained-release /controlled-release preparation while CL/F and V/F were 26.6%, 9.5% in nifedipine immediate release preparation.