Abstract:

This study aimed to investigate the in vivo pharmacokinetics of thiamphenicol powder in chickens after oral administration. After the pharmacokinetic parameters were obtained, the rationality of the recommended oral dosing regimen of thiamphenicol powder in chickens was revaluated by Monte Carlo simulation (MCS). Three groups were set: thiamphenicol 10 mg·kg^-1 BW intravenous injection group, and thiamphenicol powder 10 and 20 mg·kg^-1 BW oral gavage groups. Blood samples were collected at a scheduled time and the concentration of thiamphenicol in chicken plasma was determined by a verified HPLC method. The pharmacokinetic parameters of thiamphenicol in chickens were fitted, and the epidemiological cut-off value (ECOFF) of thiamphenicol against Pasteurella multocida was established. Then the PK/PD cut-off values at bacteriostatic, bactericidal, and eradication of thiamphenicol against Pasteurella multocida were used to predicate the target attainment rate (TAR) by MCS. The effective dose was calculated to optimize the clinical dosage regimen. The results showed that AUC_inf, T_1/2Z, CL and V_C were (14.21±5.69) μg·h·mL^-1, (1.85±1.20) h, (803.11±297.78) mL·(kg·h)^-1, and (403.63±93.74) mL·kg^-1, respectively, after intravenous administration of 10 mg·kg^-1 BW. After oral administration of 10 and 20 mg·kg^-1 BW, the C_max were (1.70±0.27) μg·mL^-1 and (3.36±0.98) μg·mL^-1, the T_max were (1.30±0.48) h and (1.50±0.53) h, the AUC_inf were (5.01±0.80) μg·h·mL^-1 and (12.38±3.21) μg·h·mL^-1, T_1/2Z were (2.25±1.03) h and (2.31±1.00) h, and oral bioavailability were 33.84% and 43.08%, respectively. The TAR that bacteriostatic, bactericidal, and eradication of Pasteurella multocida under ECOFF (2 μg·mL^-1) by the low and high doses (10 and 20 mg·kg^-1 BW) of thiamphenicol powder were 26.96% and 86.03%, 10.77% and 58.89%, 9.40% and 49.62%, respectively, all of which were less than 90%. The 24 h dosage for bacteriostatic, bactericidal, and eradication was calculated as 43.1, 66.4 and 78.1 mg·kg^-1 BW, respectively. These results indicate that the current dosage regimen cannot realize the bacteria cure of chicken Pasteurella multocida infection and that at least 45 mg kg^-1 BW is necessary for effectiveness.

Key words: thiamphenicol powder, PK/PD, Pasteurella multocida, efficacy revaluation