Population Pharmacokinetics Analysis of Mitiglinide in Chinese Healthy Volunteers / 中国药师

ABSTRACT

Objective:To establish the population pharmacokinetics model of mitiglinide given by oral route in Chinese healthy volunteers using nonlinear mixed effect model (NONMEM), investigate the pharmacokinetic characteristics of mitiglinide in Chinese healthy people to evaluate the factors that can influence the clinical pharmacokinetics of mitiglinide .Methods: Clinical data from 22 healthy volunteers were collected and the experiment was with single-dose administration.The volunteers were given 10 mg mitiglinide calcium orally and mitiglinide plasma concentration was determined by LC-MS/MS.The data was analyzed by the first order conditional estimation, and the influences of fixed effect factors such as demographic index and biochemical index were quantitatively evaluated . The population pharmacokinetics model of mitiglinide was established , and the result was verified by using the VPC and self-test meth-od.Results:The result showed that mitiglinide pharmacokinetics was fit single-compartment model .The inter-individual variability could be described by an exponential model .The typical values including central volume of distribution , clearance and absorption con-stant was 2.4 L· h-1(24％), 9.82 L(4％) and 6.46 h-1(14％), respectively.The clearance was influenced by creatinine clear-ance rate , and the absorption constant was influenced by ALT .Conclusion:The population pharmacokinetic parameters were mainly influenced by creatinine clearance rate and ALT .The established population pharmacokinetics model can explain the reasons for the in -dividual variation in the plasma concentration of mitiglinide , which can be used to guide the clinical administration of Chinese people .