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(z)) of 4.27 ± 0.99 L /kg. Mean valnemulin t(1/2β)(h), Cl(β)(L /h /kg), V(ss)(L /kg) and AUC((0-∞))(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(max) of 2.2 μg/mL achieved at 0.43 h (t(max)), 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.

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.

This study was performed in 145 pigs to develop a population pharmacokinetics (PPK) model by i.m. administration of cefquinome (CEQ) at the dose of 2 mg/kg in the neck muscle. Serum physiological and biochemical parameters for each pig were determined before administration. After administration, 2-4 samples were collected at random, with the sampling point evenly distributed in the three periods (<1 h, 1-4 h and >4 h). The plasma concentration of CEQ was determined by high performance liquid chromatography with UV detector. The pharmacostatistical analyses of concentration-time data, weight, age, gender, serum physiological and biochemical parameters were performed with nonlinear mixed effect modeling (NONMEM). A one-compartmental model with first-order absorption and elimination adequately described the data from the study group. The optimal random effect model of pharmacokinetics parameters was of log-normal distribution and the residual errors assumed a mixed-type model (proportional and additive) to best explain intra-individual variability. Covariate analysis showed that body weight is positively correlated with apparent volume of distribution (V/F) and body clearance (CL/F). The typical PPK parameters of Ka , CL, and V were 0.564/h, 5.15 L/h, and 1.36 L, respectively.