Search

The pharmacokinetics and bioavailability of cefquinome in Beagle dogs were determined by intravenous ( IV), intramuscular ( IM) or subcutaneous ( SC) injection at a single dose of 2 mg/kg body weight ( BW). The minimum inhibitory concentrations ( MIC) of cefquinome against 217 Escherichia coli isolated from dogs were also investigated. After IV injection, the plasma concentration-time curve of cefquinome was analyzed using a two-compartmental model, and the mean values of t1/2α (h), t1/2β (h), Vss (L/kg), ClB (L/kg/h) and AUC (μg·h/ mL) were 0.12, 0.98, 0.30, 0.24 and 8.51, respectively. After IM and SC administration, the PK data were best described by a one-compartmental model with first-order absorption. The mean values of t1/2Kel, t1/2Ka, tmax (h), Cmax (μg/ mL) and AUC (μg·h/ mL) were corresponding 0.85, 0.14, 0.43, 4.83 and 8.24 for IM administration, 0.99, 0.29, 0.72, 3.88 and 9.13 for SC injection. The duration of time that drug levels exceed the MIC (%T > MIC) were calculated using the determined MIC90 (0.125 μg/ mL) and the PK data obtained in this study. The results indicated that the dosage regimen of cefquinome at 2 mg/kg BW with 12-h intervals could achieve %T > MIC above 50% that generally produced a satisfactory bactericidal effect against E. coli isolated from dogs in this study. [ABSTRACT FROM AUTHOR]

To estimate the valnemulin pharmacokinetic profile in a swine population and to assess a dosage regimen for increasing the likelihood of optimization. This study was, respectively, performed in 22 sows culled by p.o. administration and in 80 growing-finishing pigs by i.v. administration at a single dose of 10 mg/kg to develop a population pharmacokinetic model and Monte Carlo simulation. The relationships among the plasma concentration, dose, and time of valnemulin in pigs were illustrated as C i, v = X0(8.4191 × 10-4 × e−0.2371 t + 1.2788 × 10−5 × e−0.0069 t) after i.v. and C p. o = X0(−8.4964 × 10−4 × e−0.5840 t + 8.4195 × e−0.2371 t + 7.6869 × 10−6 × e−0.0069 t) after p.o. Monte Carlo simulation showed that T> MIC was more than 24 h when a single daily dosage at 13.5 mg/kg BW in pigs was administrated by p.o., and MIC was 0.031 mg/L. It was concluded that the current dosage regimen at 10-12 mg/kg BW led to valnemulin underexposure if the MIC was more than 0.031 mg/L and could increase the risk of treatment failure and/or drug resistance. [ABSTRACT FROM AUTHOR]

A multi-compartment physiologically based pharmacokinetic ( PBPK) model to describe the disposition of cyadox ( CYX) and its metabolite quinoxaline-2-carboxylic acid ( QCA) after a single oral administration was developed in rats (200 mg/kg b.w. of CYX). Considering interspecies differences in physiology and physiochemistry, the model efficiency was validated by pharmacokinetic data set in swine. The model included six compartments that were blood, muscle, liver, kidney, adipose, and a combined compartment for the rest of tissues. The model was parameterized using rat plasma and tissue concentration data that were generated from this study. Model simulations were achieved using a commercially available software program ( ACSLXLibero version 3.0.2.1). Results supported the validity of the model with simulated tissue concentrations within the range of the observations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, adipose, and muscles in rats were 0.98, 0.98, 0.98, 0.99, and 0.95, respectively. The rat model parameters were then extrapolated to pigs to estimate QCA disposition in tissues and validated by tissue concentration of QCA in swine. The correlation coefficients between the predicted and observed values were over 0.90. This model could provide a foundation for developing more reliable pig models once more data are available. [ABSTRACT FROM AUTHOR]

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]

A Mycoplasma gallisepticum- Escherichia coli mixed infection model was developed in broiler chickens, which was applied to pharmacokinetics of valnemulin in the present experiment. The velogenic M. gallisepticum standard strain S6 was rejuvenated to establish the animal model, and the wild E. coli strain O78 was injected as supplementary inoculum to induce chronic respiratory disease in chickens. The disease model was evaluated based on its clinical signs, histopathological examination, bacteriological assay, and serum plate agglutination test. The pharmacokinetics of valnemulin in infected chickens was determined by intramuscular (i.m.) injection and oral administration ( per os, p.o.) of a single dose of 10 mg/kg body weight (BW). Plasma samples were analyzed by liquid chromatography-tandem mass spectrometry. The plasma concentration-time curve of valnemulin was analyzed using the noncompartmental method. After the i.m. administration, the mean values of Cmax, Tmax, AUClast, MRT, CLβ/ F, Vz/ F, and t1⁄2β, were 27.94 μg/mL, 1.57 h, 171.63 μg·h/mL, 4.51 h, 0.06 L/h/kg, 0.56 L/kg, and 6.50 h, respectively. By contrast, the corresponding values after p.o. administration were 5.93 μg/mL, 7.14 h, 47.60 μg·h/mL, 9.80 h, 0.22 L/h/kg, 3.35 L/kg, and 10.60 h. The disposition of valnemulin was retarded in infected chickens after both modes of extravascular administration as compared to the healthy controls. More attention should be given to monitoring the therapeutic efficacy and adverse effects of mixed infection because of higher required plasma drug concentration and enlarged AUC with valnemulin treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Yuan, L. G., Luo, X. Y., Zhu, L. X., Wang, R., Liu, Y. H. A physiologically based pharmacokinetic model for valnemulin in rats and extrapolation to pigs. J. vet. Pharmacol. Therap., 224-231. A flow-limited, physiologically based pharmacokinetic (PBPK) model for predicting the plasma and tissue concentrations of valnemulin after a single oral administration to rats was developed, and then the data were extrapolated to pigs so as to predict withdrawal interval in edible tissues. Blood/tissue pharmacokinetic data and blood/tissue partition coefficients for valnemulin in rats and pigs were collected experimentally. Absorption, distribution and elimination of the drug were characterized by a set of mass-balance equations. Model simulations were achieved using a commercially available software program. The rat PBPK model better predicted plasma and tissue concentrations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, lung and muscle were 0.96, 0.94, 0.96, 0.91 and 0.91, respectively. The rat model parameters were extrapolated to pigs to estimate valnemulin residue withdrawal interval in edible tissues. Correlation ( R) between predicted and observed liver, kidney and muscle were 0.95, 0.97 and 0.99, respectively. Based on liver tissue residue profiles, the pig model estimated a withdrawal interval of 10 h under a multiple oral dosing schedule (5.0 mg/kg, twice daily for 7.5 days). PBPK models, such as this one, provide evidence of the usefulness in interspecies PK data extrapolation over a range of dosing scenarios and can be used to predict withdrawal interval in pigs. [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]

The article presents a study on the pharmacokinetic characteristics of the fluoroquinolone Marbofloxacin administered via various drug routes to Muscovy ducks. The study assessed 30 healthy Muscovy ducks divided into three groups of 10 in a controlled environment, which were then examined using a parallel study design. Results showed that an oral dosage of 2.5 milligrams (mg) per kilogram (kg) is the treatment recommended for infections caused by Gram-negative bacteria in ducks.

This study was performed in 105 ill cows to determine the best practical individualized dose of enrofloxacin after i.m. (2.5 mg/kg) single-dose administration. Samples were collected from each cow at random time to ensure the percentage of samples distributed equally in the absorption phase, distribution phase, and elimination phase of the drug. Drug concentrations were determined by high-performance liquid chromatography with fluorometric detector, analyzed by population pharmacokinetic (PPK) modeling with NONMEM. The concentration–time data for enrofloxacin in plasma and ciprofloxacin were fitted to the one-compartment model with first-order absorption and elimination. The final covariate model indicated that body weight and daily milk productions have significant influence on clearance (CL) of enrofloxacin and ciprofloxacin, and the volume ( V) of distribution of enrofloxacin. The typical PPK parameters were Ka = 3.33 h−1, CL = 1.25 L/h/kg, and V = 2.98 L/kg of enrofloxacin, and the interindividual variability for CL and V were 20.2% and 24.3%, respectively, the population mean estimates of Ka, CL, and V for ciprofloxacin were 1.12 h−1, 2.36 L/h/kg, 8.20 L/kg, respectively, and their interindividual variability was 36.9%, 15.8% and 14.1%, respectively. [ABSTRACT FROM AUTHOR]