Dong-Hao Zhao and Zhan Zhang contributed equally to this work.
Population pharmacokinetics of valnemulin in swine
Version of Record online: 26 APR 2013
© 2013 John Wiley & Sons Ltd
Journal of Veterinary Pharmacology and Therapeutics
Volume 37, Issue 1, pages 59–65, February 2014
How to Cite
Population pharmacokinetics of valnemulin in swine. J. vet. Pharmacol. Therap. 37, 59–65., , , , , , ,
- Issue online: 10 JAN 2014
- Version of Record online: 26 APR 2013
- Manuscript Received: 26 MAR 2013
- Manuscript Accepted: 26 MAR 2013
- National Science Fund for Distinguished Young Scholars of China. Grant Number: 31125026
- Agro-scientific Research. Grant Number: 201203040
This study was carried out in 121 pigs to develop a population pharmacokinetic (PPK) model by oral (p.o.) administration of valnemulin at a single dose of 10 mg/kg. Serum biochemistry parameters of each pig were determined prior to drug administration. Three to five blood samples were collected at random time points, but uniformly distributed in the absorption, distribution, and elimination phases of drug disposition. Plasma concentrations of valnemulin were determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). The concentration–time data were fitted to PPK models using nonlinear mixed effect modeling (NONMEM) with G77 FORTRAN compiler. NONMEM runs were executed using Wings for NONMEM. Fixed effects of weight, age, sex as well as biochemistry parameters, which may influence the PK of valnemulin, were investigated. The drug concentration–time data were adequately described by a one-compartmental model with first-order absorption. A random effect model of valnemulin revealed a pattern of log-normal distribution, and it satisfactorily characterized the observed interindividual variability. The distribution of random residual errors, however, suggested an additive model for the initial phase (<12 h) followed by a combined model that consists of both proportional and additive features (≥12 h), so that the intra-individual variability could be sufficiently characterized. Covariate analysis indicated that body weight had a conspicuous effect on valnemulin clearance (CL/F). The featured population PK values of Ka, V/F and CL/F were 0.292/h, 63.0 L and 41.3 L/h, respectively.