Pharmacokinetics Of Thiamphenicol In Healthy And Experimentally Infected Chickens With Pasteurella Multocida

The pharmacokinetics of thiamphenicol were investigated following single intravenous (15mg/kg b.w.), and oral (30mg/kg b.w.) administration in healthy and diseased chickens experimentally infected with Pasteurella multocida .Forty chickens were randomly divided into 4 groups. Blood samples were obtained in each period within 0.5 hour before dosing ,and at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hours after dosing. The thiamphenicol concentrations in plasma were determined by reverse-high performance liquid chromatography (HPLC) with UV detector at a detective limit of 0.01mg/l. The concentration-time date of thiamphenicol in plasma were analysised with 3p87 computer program.The Pasteurella multocida(C_48-1)infection was induced by intramuscular inoculation with a dose of 8×10³ cfu/kg b.w. Clinical lowgrade signs were observed at 6 hours after the infection, and typical signs were observed at 10h after the infection. The results of clinical symptom observation , post-mortem-lead fragments examination and pathogen indentification suggested that the chicken death was caused by the acute hemorrhagic septicemia infecting Pasteurella multocida.The concentration-time date of thiamphenicol in plasma after single i.v. dosing in healthy and experimentally infected chickens are fitted to a two-compartment open model. The main pharmacokinetics parameters of thiamphenicol in healthy chickens are as follows, t_1/2α is 0.11±0.03 h, t_1/2β is 0.95±0.18 h, AUC is 11.99±0.90 mg/l·h, V(c) is 0.58±0.09 l/kg, Vd(ss) is 1.31±0.16 l/kg, CL(s) is 1.26±0.10 l/kg/h. The main pharmacokinetics parameters of thiamphenicol in infected chickens are as follows, t_1/2α is 0.12±0.04 h, t_1/2β is 1.21±0.31 h, AUC is 13.86±1.96 mg/l·h,V(c) is 0.50±0.05 l/kg, Vd(ss) is 1.34±0.24 l/kg, CL(s) is 1.10±0.13 l/kg/h. Compared to parameters in healthy chickens, some parameters, such as t_1/2β and AUC, in infected chickens are significantly higher than the ones in healthy chickens(P<0.05), some parameters,such as V(c) and CL(s), are decreased significantly(P<0.05 or 0.01), the other parameters are in the same level.The concentration-time date of thiamphenicol in plasma after single oral dosing in healthy and experimentally infected chickens are fitted to a one-compartment open model with first-order obsorption. The main pharmacokinetics parameters of thiampenicol in healthy chickens are as follows, Lagtime is 0.04±0.02h, t_1/2(ka) is 0.16±0.08 h, t_1/2(ke) is 1.64±0.22 h, T_(peak) is 0.57±0.18 h, C_(max) is 6.34±0.56μg/ml, AUC is 19.02±1.48mg/l·h, F is 79.32±6.16 %. The main pharmacokinetics parameters of thiamphenicol in infected chickens are as follows, Lagtime is 0.07±0.02 h, t_1/2(ka) is 0.54±0.26 h, t_1/2(ke) is 1.74±0.27 h, T_(peak) is 1.31±0.39 h, C_(max) is 5.28±0.73μg/ml, AUC is 21.75±1.03 mg/l·h, F is 90.70±4.30%. Compared to parameters in healthy chickens, several parameters in infected chickens, such as Lagtime, t_1/2(ka), T_(peak), AUC and F, are significantly higher than in healthy chickens(P<0.05 or 0.01), but C_(max) is decreased significantly(P<0.01).The results of the studies showed that the pharmacokinetics of thiamphenicol in healthy chickens manifested rapid absorption, wide distribution and fast elimination in the body. The bioavailability of thiamphenicol in infected chickens were higher than in healthy chickens, and the rate of absorbability and elimination decreased significantly in infected chicken.