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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. [ABSTRACT FROM AUTHOR]

Wang, R., Yuan, L.G., He, L.M., Zhu, L.X., Luo, X.Y., Zhang, C.Y., Yu, J.J., Fang, B.H., Liu, Y.H. Pharmacokinetics and bioavailability of valnemulin in broiler chickens. J. vet. Pharmacol. Therap., 247-251. The objective of this study was to investigate the pharmacokinetics and bioavailability of valnemulin in broiler chickens after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 10 mg/kg body weight (bw). Plasma samples were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic characterization was performed by non-compartmental analysis using WinNonlin program. After intravenous administration, distribution was wide with the volume of distribution based on terminal phase(V) of 4.27 ± 0.99 L /kg. Mean valnemulin t(h), Cl(L /h /kg), V (L /kg) and AUC(μg·h /mL) values were 2.85, 0.99, 2.72 and 10.34, respectively. After intramuscular administration, valnemulin was rapidly absorbed with a C of 2.2 μg/mL achieved at 0.43 h (t), and the absolute bioavailability (F) was 88.81%; and for the oral route the same parameters were 0.66 ± 0.15 μg/mL, 1.54 ± 0.27 h and 74.42%. A multiple-peak phenomenon was present after oral administration. The plasma profile of valnemulin exhibited a secondary peak during 2-6 h and a tertiary peak at 32 h. The favorable PK behavior, such as the wide distribution, slow elimination and acceptable bioavailability indicated that it is likely to be effective in chickens. [ABSTRACT FROM AUTHOR]