No abstract

Florfenicol is a fluorinated analog of thiamphenicol and has been used for treatment of animal respiratory infectious diseases with a mechanism of action of inhibiting protein synthesis of bacterial peptidyl transferase specifically on 70 S ribosomes (Cannon et al., 1990;Varma et al., 1991;Ueda et al., 1995). With modifications based on the chemical structure of chloramphenicol, florfenicol has been shown to not only circumvent the bacterial acetyltransferase-mediated drug resistance but also to ameliorate the risk of inducing drug-related aplastic anemia in humans (Syriopoulou et al., 1981;Soback et al., 1995).Pharmacokinetics of florfenicol have been described in calves, cows, broiler chickens and muscovite ducks (Varma et al., 1986;Bretzlaff et al., 1987;Lobell et al., 1994;Soback et al., 1995;el-Banna, 1998;Shen et al., 2003). Recently, florfenicol tends to be increasingly used for treating porcine pneumonias caused by Actinobacillus pleuropneumoniae (Ueda et al., 1995;Liu et al., 2003) and Pasteurella multocida (Voorspoels et al., 1999). We wished to evaluate pharmacokinetics of florfenicol in pigs following intravenous (i.v.), intramuscular (i.m.) or oral (p.o.) administration and the potential feed-effect on its oral dosing.Twelve clinically-healthy crossbred pigs (Duroc · Landrace · Yorkshire) were housed in semi-contained pens with access to water ad libitum and a commercial nonmedicated chow at scheduled times. Pharmacokinetics of florfenicol was first studied in six animals (b.w., 24.7 ± 1.0 kg), which were divided into three groups according to the Latin square design. Each group of two animals received a single dose of florfenicol at 20 mg/kg via i.v., i.m. or p.o. administration sequentially, with a 10-day washout between treatments. An injection solution of florfenicol (300 mg/mL; Huihua, Guangzhou, China) was given i.v. via the ear vein or i.m. An amylum-based powder containing 15% florfenicol (Huihua) was given orally by gavage. Blood samples of each 5 mL were collected prior to the i.v. dosing and at 0.083, 0.167, 0.25, 0.5, 0.75, 1,, 1.5, 2, 3, 4, 6, 9, 12, 15, 24, 36 and 48 h thereafter; to the i.m. dosing and at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12, 15, 24, 36 and 48 h thereafter; to the p.o. doing and at 0.083, 0.5, 0.75, 1, 1.5, 2, 3, 4, 9, 12, 15, 24, 36 and 48 h thereafter, respectively. Plasma was prepared immediately and stored at )20°C until analysis.The effect of feed intake on the pharmacokinetics of florfenicol was next studied in six pigs (b.w., 15.3 ± 1.2 kg). Two groups of three animals were designated to undergo either fasting for 16 h or feeding for 1 h with the standard diet before they were orally given a single dose of florfenicol at 20 mg/kg. Blood samples were taken immediately prior to the drug treatment and at 0. 083, 0.5, 0.75,1, 2, 3, 4, 9, 12, 15, 24, 36 and 48 h thereafter, followed by the immediate preparation of plasma. After a 10-day washout, animals were crossover to the alternative condition followed a repetition of the above pharmacokinetic study....

Tissue pharmacokinetic data could be evidence for regime designing of florfenicol in treatment of porcine pleuropneumonia.

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

The pharmacokinetics of sulfadimidine (SDM) and its N4-acetyl metabolite (N4SDM) were investigated after intravenous bolus injection of a single dose (200 mg/kg) of SDM in normal and diseased New Zealand white rabbits. The apparent distribution volume at steady state, total body clearance and elimination half-life of SDM in normal animals were 0.7 +/- 0.3 l/kg, 0.57 +/- 0.24 l/kg/h and 1.6 +/- 1.3 h, respectively. Of the administered dose, 62.1% was metabolized by N4-acetylation, and 12.7 +/- 1.1 and 2.8 +/- 1.8% of the dose was excreted as free drug by the kidney and gastrointestinal tract, respectively. The 'apparent' formation and elimination half-lives of N4SDM were 0.6 +/- 0.4 and 2.2 +/- 1.1 h, respectively. The metabolite was eliminated mainly by excretion through the kidney. There was no significant effect of acute pasteurellosis on the pharmacokinetics of either SDM or N4SDM in rabbits.

Plasma and cerebrospinal fluid (CSF) pharmacokinetics of meperidine were investigated after intramuscular (i.m.) or intravenous (i.v.) administration at a dose of 5 mg/kg in adult goats. After i.m. dosing, the plasma profile was best described by a one-compartment open model. In healthy (n = 16) and post-operative (n = 16) goats, the parameters were, respectively: tmax 8.3 +/- 3.9 and 9.2 +/- 5.5 min, Vd 2.763 +/- 1.231 and 3.929 +/- 2.101 l/kg, Clb 0.125 +/- 0.036 and 0.087 +/- 0.025 l/kg/min, Ke 0.0563 +/- 0.0358 and 0.0271 +/- 0.0136 min-1. The plasma profile was best fitted by a two-compartment open model following i.v. injection. In this case, the parameters for healthy (n = 7) and post-operative (n = 13) goats were, respectively: Vd 5.212 +/- 1.992 and 5.085 +/- 2.288 l/kg, Clb 0.096 +/- 0.028 and 0.075 +/- 0.026 l/kg/min, beta 0.0211 +/- 0.0093 and 0.0160 +/- 0.0052 min-1. There were, however, a few individuals with a prolonged elimination phase. Bioavailability of i.m. meperidine was 66.5 +/- 15.8% in healthy (n = 6) goats, but much higher in postoperative (n = 10) ones at 94.6 +/- 30.0%. Meperidine diffused into and out of CSF according to a first-order rate process. The time-course of CSF drug concentration was simulated by a biexponential function. CSF kinetic parameters of i.m. meperidine for healthy (n = 7) and postoperative (n = 13) goats were: elimination rate constant (K(ef)) 0.0269 +/- 0.0131 and 0.0305 +/- 0.0177 min-1, peak CSF concentration time (Tmaxf) 15.9 +/- 5.0 and 17.0 +/- 6.9 min. For the i.v. dosed healthy (n = 6) and postoperative (n = 8) animals, K(ef) was 0.0408 +/- 0.0107, 0.0414 +/- 0.0123 min-1 and Tmaxf was 10.0 +/- 5.0 and 7.7 +/- 2.5 min, respectively. It was demonstrated that an obviously lower peak concentration can be reached significantly later in CSF than in plasma, and the kinetic behaviour of meperidine in plasma is different from that in the CSF, indicating meperidine analgesia might not be predicted by simple extrapolation from the kinetic data.

Simultaneous pharmacokinetic-pharmacodynamic (PK-PD) models of meperidine in goats were established by utilizing the P3 wave of the cerebral evoked potentials as an analgesic measurement. An effect compartment linked to the central compartment was postulated in the models. The hypothetical drug amount in the effect compartment was related to the observed analgesia through the Hill equation. After intramuscular (i.m., n = 16) and intravenous (i.v., n = 13) dosing (5 mg/kg), the elimination rate constants of meperidine in the effect compartment (Ke0) were 0.3744 +/- 0.2546 and 0.1123 +/- 0.0428 min-1, drug concentrations in the effect compartment generating half maximal analgesia (EC(50)) were 0.70 +/- 0.33 and 0.41 +/- 0.26 microgram/ml, the maximal effects (Emax) were 89.63 +/- 15.63 and 85.92 +/- 9.64%, and the Hill coefficients (S) were 2.61 +/- 1.21 and 2.37 +/- 1.15, respectively. Ke0 and EC(50) with i.m. dosing were significantly greater than with i.v. injection. However, administration route had no influence on S, Emax and the total amount of effect (AUE). The predicted peak effect (Emax) of 64.44 +/- 14.64 and 66.02 +/- 11.51% were achieved at 14.7 +/- 7.4 and 8.5 +/- 2.2 min after i.m. and i.v. dosing, respectively. Peak analgesia appeared much later than peak plasma concentration, but simultaneously with peak CSF level both after i.m. and i.v. dosing. An obvious hysteresis was demonstrated between plasma concentration and analgesic effect. This study demonstrates that meperidine analgesia can be predicted using a PK-PD model, but not by PK data alone. Both i.m. and i.v. administration routes were evaluated kinetically and dynamically.