OBJECTIVE: To determine the pharmacokinetics and milk penetration of enrofloxacin (ENR) and ciprofloxacin (CIP) in lactating rabbits and their disposition in suckling rabbits. DESIGN: Prospective cross-over study. ANIMALS: 6 lactating New Zeland White rabbits and their offspring (16 days after parturition). PROCEDURE: Serial plasma and milk samples were assayed by use of a high-performance liquid chromatography technique. In vitro protein binding in plasma and skim milk was measured by ultrafiltration. Skim-to-whole milk ratio also was determined. The time course of ENR and CIP was fitted by nonlinear least squares regression analysis, and the pharmacokinetic variables were compared. RESULTS: The time courses of ENR and CIP in plasma were similar in lactating adult rabbits (mean body clearances, 23.9 and 27.2 ml/min/kg of body weight, for ENR and CIP, respectively). Observed milk-to-plasma ratios (M/P) were determined, using the area under the milk and plasma concentration versus time profiles (ENR, 2.59; CIP, 3.61). Predicted M/P (ENR, 6.35; CIP, 3.04) were calculated from in vitro measurements. Body clearance calculated for ENR and CIP in suckling rabbit pups involved a decrease of 80 and 74%, respectively, over that found in lactating animals. CONCLUSIONS: Observed CIP M/P were correlated to predicted values, which strengthens the argument that CIP passes into the milk by nonionic diffusion. The lack of correlation between observed and predicted ENR M/P pointed out that ENR undergoes faster elimination from milk than that predicted by the diffusional model. Diminished elimination capacity observed in suckling rabbits would result in greater exposure than that predicted from concentrations alone.
OBJECTIVE: To determine the pharmacokinetics and milk penetration of enrofloxacin (ENR) and ciprofloxacin (CIP) in lactating rabbits and their disposition in suckling rabbits. DESIGN: Prospective cross-over study. ANIMALS: 6 lactating New Zeland White rabbits and their offspring (16 days after parturition). PROCEDURE: Serial plasma and milk samples were assayed by use of a high-performance liquid chromatography technique. In vitro protein binding in plasma and skim milk was measured by ultrafiltration. Skim-to-whole milk ratio also was determined. The time course of ENR and CIP was fitted by nonlinear least squares regression analysis, and the pharmacokinetic variables were compared. RESULTS: The time courses of ENR and CIP in plasma were similar in lactating adult rabbits (mean body clearances, 23.9 and 27.2 ml/min/kg of body weight, for ENR and CIP, respectively). Observed milk-to-plasma ratios (M/P) were determined, using the area under the milk and plasma concentration versus time profiles (ENR, 2.59; CIP, 3.61). Predicted M/P (ENR, 6.35; CIP, 3.04) were calculated from in vitro measurements. Body clearance calculated for ENR and CIP in suckling rabbit pups involved a decrease of 80 and 74%, respectively, over that found in lactating animals. CONCLUSIONS: Observed CIP M/P were correlated to predicted values, which strengthens the argument that CIP passes into the milk by nonionic diffusion. The lack of correlation between observed and predicted ENR M/P pointed out that ENR undergoes faster elimination from milk than that predicted by the diffusional model. Diminished elimination capacity observed in suckling rabbits would result in greater exposure than that predicted from concentrations alone.