Residue depletion of marbofloxacin in broiler chicken after oral administration at 5 mg/kg/day for three consecutive days was studied in this study. The areas under the concentration-time curve from 0 h to ∞ (AUC0-∞ s) of marbofloxacin in tissues and plasma were used to calculate tissue/plasma partition coefficients (PX s). Based on PX s and the other parameters derived from published studies, a flow-limited physiologically based pharmacokinetics (PBPK) model was developed to predict marbofloxacin concentrations, which were then compared with those derived from the residue depletion study so as to validate this model. Considering individual difference in drug disposition, a Monte Carlo simulation included 1000 iterations was further incorporated into the validated model to generate a population PBPK model and to estimate the marbofloxacin residue withdrawal times in edible tissues. The withdrawal periods were compared to those derived from linear regression analysis. The PBPK model presented here successfully predicted the measured concentrations in all tissues. The withdrawal times in all edible tissues derived from the population PBPK model were longer than those from linear regression analysis, and based on the residues in kidney, a withdrawal time of 4 days was estimated for marbofloxacin after oral administration at 5 mg/kg/day for three consecutive days. It was shown that population PBPK model could be used to accurately predict marbofloxacin residue withdrawal time in edible tissues in broiler chickens.

No abstract

No abstract

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.

No abstract