nfluence of nimesulide administration on rational selection of ceftiofur for its use as antimicrobial agent against past
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Date
2014
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Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana
Abstract
Pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of the ceftiofur crystalline free acid (CCFA) was conducted in healthy non-lactating goats following a single subcutaneous injection (6.6 mg/kg) and CCFA with nimesulide (2.5 mg/kg). The PK data obtained were typical as expected with long acting formulations with mean terminal half-lives of ceftiofur+desfuroylceftiofur (DFC) of 48.6h and 54.1h post CCFA and CCFA+nimesulide administration, respectively. Extensive penetration of drug into biological fluids and tissues of goats was indicated by large volume of distribution (Vd/F= 2.16-2.17 L/kg) after both administrations. In vitro protein binding of ceftiofur in goat plasma was 46.6%. The minimum bactericidal concentration (MBC=0.20µg/ml) of ceftiofur for P. multocida was just two folds of MIC which suggested bactericidal activity of drug. Time-kill curves (in vitro) and ex-vivo after administration of CCFA and CCFA+nimesulide, demonstrated timedependent bactericidal action against P. multocida. Mutant prevention concentration (MPC) of ceftiofur was 9-10×MIC against P. multocida. PK-PD integration provided mean values for AUC0-24h/MIC and T > MIC, respectively, of 302h and 107% against P. multocida (MIC=0.20 µg/ml) after CCFA administration. Based on the MPC=1.40 µg/mL for P.multocida, the PK-PD indices viz., T > MPC and AUC0-24h/MPC that correlate better with probability of emergence of resistant subpopulation against ceftiofur were 25% and 43h, respectively. The percentage T > MIC and AUC0-24h/ MIC were 125 and 307h, respectively, following CCFA+ nimesulide administration. PK-PD parameters were similar and predicted the successful outcome and protection from the emergence of resistance following CCFA (6.6 mg/kg) alone and CCFA+nimesulide administration for pneumonia in goats against P. multocida