FLORFENICOL PHARMACOKINETICS IN CALVES FOLLOWING A SINGLE SUBCUTANEOUS INJECTION

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Abstract

This study was a part of a larger project using pharmacokinetic-pharmacodynamic (PK-PD) modelling to evaluate antimicrobial drugs in calf pneumonia. Ten healthy animals received 40 mg/kg florfenicol by a single subcutaneous (SC) injection and at pre-determined time points (0-120 h), serum, exudate and transudate samples were collected using a tissue cage model. Florfenicol concentrations in samples were determined by a validated HPLC method and then PK parameters of florfenicol in biological fluids of calves were calculated. Florfenicol PK data were used for PK-PD integration and for determination of average concentrations/minimal inhibitory concentration (Cave/MIC) ratios of M. hemolytica and P. multocida in 24 h periods following injection. In PK modelling, a two-compartmental model for serum and a one-compartmental model for exudate and transudate were used. Comparing the PK parameters of three biological fluids indicated that mean serum Cmax (5.91 µg/ml) was higher and mean serum Tmax (2.28 h) was much shorter than those of exudate (3.39 µg/ml, 17.2 h) and transudate (2.84 µg/ml, 17.9 h). These results suggest that florfenicol readily penetrates and distributes in interstitial fluids and achieves concentrations about half of the serum levels in tissue cage fluids. PK- PD integration of florfenicol in serum of calves showed desirable values for AUC 0-24 h/MIC in M. hemolytica and P. multocida, 151.8 and 183.3 h,...

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