Establishment of population pharmacokinetics model of nebivolol in Chinese healthy volunteers

To establish population pharmacokinetics model of nebivolol given by oral route in Chinese healthy volunteers using nonlinear mixed effect model (NONMEM),thus evaluating the factors that could influence clinical pharmacokinetics of nebivolol.Clinical data from 25 healthy volunteers were collected and the experiments _{included single-dose and multiple-dose administration.Volunteers were given 5 mg nebivolol orally and plasma concentrations of the drug were determined by LC-MS/MS.The population pharmacokinetic modeling was performed with NONMEM program and estimated by bootstrap procedure.The results showed that two-compartment model had fit for nebivolol pharmacokinetics.Inter-individual variability was described by multiplicative model.Typical values of central volume of distribution and clearance were 1.84×10³ L and 7.68×10² L/h.The population pharmacokinetic parameters were mainly influenced by body weight,diastolic blood pressure,blood urea nitrogen and phenotype.The parameters estimated from nonparametric bootstrap procedure were comparable to those from NONMEM.The established population pharmacokinetics model could explain the reasons for the plasma concentration of individual variations of nebivolol,which could be used to guide clinical administration to Chinese people.}