EFFECT OF LACTATION ON SINGLE-DOSE PHARMACOKINETICS OF NORFLOXACIN NICOTINATE IN EWES

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 weigh t) during nursing, 1 day after weaning, and 1 month after weaning. Blo od and milk samples were collected at different time intervals followi ng dosing, and norfloxacin concentrations were determined by a highper formance liquid chromatography assay. The serum drug concentration ver sus time data were analyzed by a noncompartmental approach which was b ased 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 afte r 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 volume s 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 co ncentrations were up to 40 times higher than the corresponding concent rations 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 appeare d to be in the milk. Therapeutic concentrations of norfloxacin could b e detected in the sera of suckling lambs, implicating that fluoroquino lone therapy should be discouraged during breast feeding. In lactating ewes and in ewes with full udders, moment analysis calculations did n ot show a significant difference between the system moment mean reside nce time and the system matrix mean residence time values. Thus, the p harmacokinetics 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 t he existence of a distinguishable milk compartment. Milk secretion see med to act as one of the clearance processes of the drug when milk was continuously removed.