Pharmacokinetic-pharmacodynamic integration of marbofloxacin after single and repeated intravenous administration in goats.

The single dose pharmacokinetics (PK) of marbofloxacin was compared with repeated intravenous (IV) administrations in six healthy goats at the dose rate of 2 mg/kg body weight at 24 h interval for 5 days. Blood samples were collected at times: 5, 15, 30 min and 1, 2, 4, 6, 9, 12, 24, 36, 48 and 72 h post drug administration. Plasma drug concentrations were determined by High Performance Liquid Chromatography and concentration-time data were subjected to non-compartment analysis. The MIC and MBC of marbofloxacin against Escherichia (E.) coli and Pasteurella (P.) multocida in Mueller Hinton Broth were determined by broth microdilution method. The t _1/2elm  = 4.37 ± 0.18 h and Cl _B  = 0.29 ± 0.01 following single administration were not significantly different from t _1/2elm  = 5.11 ± 0.22 h and Cl _B  = 0.26 ± 0.01 mL/kg/h after repeated administrations of marbofloxacin. Accumulation index (AI = 1.1) indicated no accumulation of marbofloxacin following repeated IV administrations up to 5 days. The respective MICs of marbofloxacin against E. coli and P. multocida were 0.03 μg/mL and 0.4 μg/mL. The AUC _0-24h /MIC ratios were 226.64 ± 7.21 h for E. coli and 16.99 ± 0.541 h for P. multocida. PK/PD integration indicated that marbofloxacin daily dose of 2 mg/kg is appropriate for treating E. coli (MIC ≤ 0.03 μg/mL) infections. However, a higher dose of 6 mg/kg/day is suggested to obtain clinical cure against diseases caused by P. multocida having MIC ₉₀  = 0.12 μg/mL in goat species.
(Published by Elsevier Ltd.)