Cefquinome (CFQ) and amoxicillin (AMO) are beta-lactam antibiotics, belonging to the groups of cephalosporin and penicillin, respectively. CFQ and AMO are intended for the treatment of respiratory infection diseases, caused by Mannheimia haemolytica and Pasteurella multocida and for the treatment of mastitis in livestock. The aim of this study was to obtain and integrate pharmacokinetic (PK) and pharmacodynamics (PD) data of CFQ and AMO in the goats. Methods: The pharmacokinetic profile of CFQ and AMO in goats was investigated following intravenous (i.v.) and intramuscular (i.m.) administration at the doses of 1 mg/kg and 15 mg/kg, respectively. At the same time, the minimum inhibition (MIC) and minimum bactericidal (MBC) concentrations of CFQ and AMO against two reference strains of Mannheimia haemolytica and Pasteurela multocida were determined in cation-adjusted Mueller-Hinton Broth (MHB) and goat blood plasma. The bactericidal activity of CFQ and AMO was tested against Mannheimia haemolytica and Pasteurella multocida using the time killing method. Results: After i.v. administration of CFQ, the pharmacokinetics of CFQ indicated a small volume of distribution (Vss=0.204?0.02 L), a rapid clearance (2.433?0.59 mL/min) and half-life of 1.36 ? 0.2 h. After i.v. administration of AMO, the short terminal half-life (t1/2z) of 2.0 ? 0.47 h was the net result of ratio of the relatively small volume of distribution to the total clearance. After i.m. dosing absorption of CFQ was complete (F?100) and rapid and terminal half-life was 1.54?1.4 h. However, after i.m. administration of AMO, the half-life in goats (7.89?2.26 h) was much higher than after i.v. administration of AMO. The difference in half-lives between i.v. and i.m. administration of AMO suggest that the i.m administration of AMO in goats produce a flip-flop phenomenon. In broth MIC and MBC of AMO against M. haemolytica were 0.188 ?g mL-1 and against P. multocida were 0.250 ?g mL-1. MIC and MBC of AMO against M. haemolytica in goat plasma were MIC=MBC=0.188 ?g mL-1 and against P. multocida in blood plasma of goats were MIC=MBC=0.375 ?g mL-1. MIC and MBC of CFQ, when determined in MHB, were 0.047 ?g mL-1, against M. haemolytica and P. multocida. MIC and MBC of CFQ against M. haemolytica in goat plasma were 0.094 ?g mL-1. The respective value against P. multocida was MIC= 0.047 and MBC= 0.094 ?g mL-1 in goat plasma. MIC and MBC data against two reference strains M. haemolytica and P. multocida indicated that the AMO generally exhibited higher MIC and MBC when compared with CFQ. CFQ and AMO were shown to be time dependent bactericidal antibiotics against target pathogens and the killing occurring at a concentration close to the MIC. The rate of killing was not significantly influenced by the increase of antibiotic concentration. Conclusions:Taking into consideration the PK and PD parameter of AMO in goats, the concentration of the drug in the plasma remain above the MIC (=0.375 ?g/mL) of M. haemolytica and P. multocida in the goats for 12 hours after i.m. administration, and it can be concluded that a once-daily amoxicillin i.m. administration at the dose of 15 mg/kg b.w, yields therapeutically effective drug levels. Furthermore, according to PK analysis and PD data of CFQ, it can be concluded that, for susceptible bacteria, a twice-daily cefquinome i.m. administration, at the dose of 1 mg/kg b.w., will yields therapeutically effective drug levels.

Username
Password