In a three-way crossover trial, six healthy Finnish-Merino-Awassi ewes were given a single
intravenous injection of
norfloxacin nicotinate (in a dose equivalent to 25 mg of
norfloxacin base per kg of
body weight) during nursing, 1 day after weaning, and 1 month after weaning. Blood and milk samples were collected at different time intervals following dosing, and
norfloxacin concentrations were determined by a high-performance liquid chromatography assay. The serum
drug concentration versus time data were analyzed by a noncompartmental approach which was based on the statistical-moment theory. The total body clearance values were 4.2 +/- 1.3 (injection during nursing), 1.6 +/- 0.3 (injection 1 day after weaning), and 3.1 +/- 0.8 ml/min/kg (injection 1 month after weaning). The mean residence times were 335 +/- 83, 797 +/- 129, and 481 +/- 102 min and terminal half-lives were 266 +/- 51, 603 +/- 94, and 372 +/- 68 min for the respective treatments. The estimated volumes of distribution at steady state were 1.3 +/- 0.1, 1.2 +/- 0.1, and 1.4 +/- 0.2 liter/kg for the respective treatments. Milk
norfloxacin concentrations were up to 40 times higher than the corresponding concentrations in serum during lactation. Accordingly, in ewes with 1.5 liter of milk in the udder more than half of the
drug in the animal appeared to be in the milk. Therapeutic concentrations of
norfloxacin could be detected in the sera of suckling lambs, implicating that
fluoroquinolone therapy should be discouraged during breast feeding. In lactating ewes and in ewes with full udders, moment analysis calculations did not show a significant difference between the system moment mean residence time and the system matrix mean residence time values. Thus, the pharmacokinetics of
norfloxacin in the three groups could be described by the classical two-compartment open-body model with input and output occurring from the central compartment. The results did not support the existence of a distinguishable milk compartment. Milk secretion seemed to act as one of the clearance processes of the
drug when milk was continuously removed.