Pharmacokinetic and pharmacodynamic characterization of ceftiofur crystalline-free acid following subcutaneous administration in domestic goats.

ABSTRACT

Pharmacokinetic (PK)-pharmacodynamic (PD) integration of crystalline ceftiofur-free acid (CCFA) was established in six healthy female goats administered subcutaneously (s.c.) on the left side of the neck at a dosage of 6.6 mg/kg body weight. Serum concentrations of ceftiofur and desfuroylceftiofur (DFC) were determined using high-performance liquid chromatography. Mutant prevention concentration (MPC), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ceftiofur were determined for Pasteurella (P.) multocida. Mean terminal half-life and mean residence time of ceftiofur + DFC were 48.6 h and 104 h, respectively. In vitro plasma protein binding of ceftiofur was 46.6% in goats. The MIC and MBC values of ceftiofur were similar in serum and MHB and a very small difference between these values confirmed bactericidal activity of drug against P. multocida. In vitro and ex vivo time-kill curves for P. multocida demonstrated a time-dependent killing action of drug. Considering target serum concentration of 0.20 µg/mL, PK-PD values for AUC24 h /MIC90 and T > MIC90 , respectively, were 302 h and 192 h against P. multocida. A MPC/MIC ratio of 10-14 indicated that selective pressure for proliferation of resistant mutants of P. multocida is minimal after CCFA single-dose administration. Based on MPC = 1.40 µg/mL for P. multocida, the PK-PD indices, viz. T > MPC and AUC24 /MPC, were 48 h and 43 h, respectively. The data suggested the use of single dose (6.6 mg/kg, s.c.) of CCFA in goats to obtain clinical and bacteriological cure of pneumonia due to P. multocida.