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Population pharmacokinetics of valnemulin in swine
Author(s) -
Zhao D. H.,
Zhang Z.,
Zhang C. Y.,
Liu Z. C.,
Deng H.,
Yu J. J.,
Guo J. P.,
Liu Y. H.
Publication year - 2014
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12054
Subject(s) - nonmem , pharmacokinetics , population , chemistry , distribution (mathematics) , absorption (acoustics) , pharmacology , chromatography , mathematics , medicine , physics , mathematical analysis , environmental health , acoustics
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 G 77 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 K a , V / F and CL / F were 0.292/h, 63.0 L and 41.3 L/h, respectively.