Comparative pharmacokinetics of diaveridine in pigs and chickens following single intravenous and oral administration.

Comparative pharmacokinetic profiles of diaveridine following single intravenous and oral dose of 10 mg/kg body weight in healthy pigs and chickens were investigated, respectively. Concentrations of diaveridine in plasma samples were determined using a validated high-performance liquid chromatography-ultraviolet (HPLC-UV) method. The concentration-time data were subjected to noncompartmental kinetic analysis by WinNonlin program. The corresponding pharmacokinetic parameters in pigs or chickens after single intravenous administration were as follows, respectively: t1/2ß (elimination half-life) 0.74 ± 0.28 and 3.44 ± 1.07 h; Vd (apparent volume of distribution) 2.70 ± 0.99 and 3.86 ± 0.92 L/kg; ClB (body clearance) 2.59 ± 0.62 and 0.80 ± 0.14 L/h/kg; and AUC0-∞ (area under the blood concentration vs. time curve) 4.11 ± 1.13 and 12.87 ± 2.60 µg∙h/mL. The corresponding pharmacokinetic parameters in pigs or chickens after oral administration were as follows, respectively: t1/2ß 1.78 ± 0.41 and 2.91 ± 0.57 h; Cmax (maximum concentration) 0.43 ± 0.24 and 1.45 ± 0.57 µg/mL; Tmax (time to reach Cmax ) 1.04 ± 0.67 and 3.25 ± 0.71 h; and AUC0-∞ 1.33 ± 0.55 and 9.28 ± 2.69 µg∙h/mL. The oral bioavailability (F) of diaveridine in pigs or chickens was determined to be 34.6% and 72.2%, respectively. There were significant differences between the pharmacokinetics profiles in these two species.

Pharmacokinetics and ex vivo pharmacodynamics of cefquinome in porcine serum and tissue cage fluids.

A tissue cage (TC) model was used to evaluate the pharmacokinetics and ex vivo pharmacodynamics of cefquinome after intravenous (IV) and intramuscular (IM) administration to piglets at 2 mg/kg bodyweight. The mean values of area under the concentration-time curve (AUC) were 21.28 (IV) and 21.37 (IM) µg h/mL for serum, and 17.40 (IV) and 16.57 (IM) µg h/mL for TC fluid (TCF), respectively. Values of maximum concentration (C(max)) were 6.15 µg/mL (serum) and 1.15 µg/mL (TCF) after IM administration. The elimination half-lives (t(1/2ß)) in TCF (10.63 h IV and 11.81 h IM) were significantly higher than those in serum (2.33 h IV and 2.30 h IM) (P<0.05). The values of AUC(TCF)/AUC(serum) (%) after IV and IM administration were 82.4% and 80.7%, respectively. The ex vivo time-kill curves were established for serum and TCF samples using Escherichia coli ATCC 25922. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values of cefquinome against E. coli were 0.030 and 0.060 µg/mL in Mueller-Hinton broth, and 0.032 and 0.064 µg/mL in both serum and TCF, respectively. The ex vivo growth inhibition data of TCF after IM administration were fitted to the sigmoid E(max) model; AUC(24h)/MIC was 35.01 h for bactericidal activity and 44.28 h for virtual eradication, respectively. The findings from this study suggest that cefquinome may be therapeutically effective in diseases of pigs caused by E. coli when used at a dose rate of 1.33 mg/kg administered every 24 h for organisms with MIC90⩽0.50 µg/mL.

Estimating tulathromycin withdrawal time in pigs using a physiologically based pharmacokinetics model.

A physiologically based pharmacokinetics model was developed to predict tulathromycin concentrations in edible swine tissues. Physiological parameters included volumes of and plasma flows through different tissues which were obtained from the literatures. The tissue/plasma partition coefficient was calculated according to the area method, and the model was validated through a comparison of predicted and observed concentrations. Withdrawal times in different tissues were predicted. The physiologically based pharmacokinetics model presented here provided accurate predictions of the observed concentrations in all tissues. The results showed that the injection site had the longest withdrawal time (21 days), followed by skin together with fat (19 days) and then kidney (10 days), lung (6 days), liver (4 days) and muscle (1 day). A withdrawal time of 21 days was finally predicted for tulathromycin in swine after a single intramuscular injection at 2.5 mg/kg body weight.

Use of a Monte Carlo analysis within a physiologically based pharmacokinetic model to predict doxycycline residue withdrawal time in edible tissues in swine.

The pharmacokinetics of doxycycline were studied following a single intravenous (I.V.) and intramuscular (I.M.) injection of 10 mg/kg into eight healthy pigs. The steady-state tissue/plasma partition coefficients were obtained via a 3-h constant rate infusion (CRI) in four pigs. Based on the results of in vivo studies and the parameters derived from published work, a physiologically based pharmacokinetic (PBPK) model was developed to predict the drug concentration in edible tissues. The predicted values were then compared with those derived from a previous study. To account for individual differences in the processes of drug metabolism and/or diffusion, a Monte Carlo (MC) run of 1000 simulations was incorporated into the PBPK model to predict the doxycycline residue withdrawal times in edible tissues in swine. The withdrawal periods were compared with those derived from linear regression analysis. The PBPK model presented here provided accurate predictions of the observed concentrations in all tissues except for the injection site. The withdrawal times in all edible tissues derived from the MC analysis were longer than those from linear regression analysis. Based on the residues in the injection site and muscle tissue, the MC analysis predicted a withdrawal time of 33 days. Here, we illustrate that MC analysis can be incorporated into the PBPK model to accurately predict doxycycline residue withdrawal time in edible tissues in swine.

Pharmacokinetics of difloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications.

Pharmacokinetics of difloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of five (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analyzed by a compartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t(1/2beta)) were 17.14 +/- 4.14, 25.79 +/- 8.10, 16.67 +/- 4.04 (pigs) and 6.11 +/- 1.50, 5.64 +/- 0.74, 8.20 +/- 3.12 h (broilers), respectively. After single i.m. and p.o. administration, difloxacin was rapidly absorbed, with peak plasma concentrations (C(max)) of 1.77 +/- 0.66, 2.29 +/- 0.85 (pigs) and 2.51 +/- 0.36, 1.00 +/- 0.21 microg/mL (broilers) attained at t(max) of 1.29 +/- 0.26, 1.41 +/- 0.88 (pigs) and 0.86 +/- 0.4, 4.34 +/- 2.40 h (broilers), respectively. Bioavailabilities (F) were (95.3 +/- 28.9)% and (105.7 +/- 37.1)% (pigs) and (77.0 +/- 11.8)% and (54.2 +/- 12.6)% (broilers) after i.m. and p.o. doses, respectively. Apparent distribution volumes(V(d(area))) of 4.91 +/- 1.88 and 3.10 +/- 0.67 L/kg and total body clearances(Cl(B)) of 0.20 +/- 0.06 and 0.37 +/- 0.10 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), the half-lives of both absorption and distribution(t(1/2ka), t(1/2alpha)) were also determined. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 5 mg/kg given intramuscularly every 24 h in pigs, or administered orally every 24 h at the dosage of 10 mg/kg in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC(90) are <0.25 microg/mL and <0.1 microg/mL respectively.

Population pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in ill cows.

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 K(a) = 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 K(a), 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.

Pharmacokinetics of sarafloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications.

Pharmacokinetics of sarafloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of 5 (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analysed by a noncompartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t1/2beta) were 3.37 +/- 0.46, 4.66 +/- 1.34, 7.20 +/- 1.92 (pigs) and 2.53 +/- 0.82, 6.81 +/- 2.04, 3.89 +/- 1.19 h (broilers), respectively. After i.m. and p.o. doses, bioavailabilities (F) were 81.8 +/- 9.8 and 42.6 +/- 8.2% (pigs) and 72.1 +/- 8.1 and 59.6 +/- 13.8% (broilers), respectively. Steady-state distribution volumes (Vd(ss)) of 1.92 +/- 0.27 and 3.40 +/- 1.26 L/kg and total body clearances (ClB) of 0.51 +/- 0.03 and 1.20 +/- 0.20 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), mean residence times (MRT), and mean absorption times (MAT) were also determined. Sarafloxacin was demonstrated to be more rapidly absorbed, more extensively distributed, and more quickly eliminated in broilers than in pigs. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 10 mg/kg given intramuscularly every 12 h in pigs, or administered orally every 8 h in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC90 are <0.25 microg/mL.