Pharmacokinetics of enrofloxacin and danofloxacin in premature calves

The aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty-four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR-IV (10 mg/kg, IV), ENR-IM (10 mg/kg, IM), DNX-IV (8 mg/kg, IV), and DNX-IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high-pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half-life (t(1/2 lambda z)) 11.16 and 17.47 hr, area under the plasma concentration-time curve (AUC(0-48)) 139.75 and 38.90 hr*mu g/ml, and volume of distribution at steady-state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr(-1) kg(-1), respectively. The PK parameters of ENR and DNX following IM injection were t(1/2 lambda z) 21.10 and 28.41 hr, AUC(0-48) 164.34 and 48.32 hr*mu g/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC(0-48CPR)/AUC(0-48ENR) ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC(0-24)/minimum inhibitory concentration (MIC) and maximum concentration (C-max)/MIC ratios for susceptible bacteria, with the MIC90 of 0.5 and 0.03 mu g/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.