Penetration of enrofloxacin and ciprofloxacin into breast milk, and pharmacokinetics of the drugs in lactating rabbits and neonatal offspring.
OBJECTIVE
To determine the pharmacokinetics and milk penetration of enrofloxacin (ENR) and ciprofloxacin (CIP) in lactating rabbits and their disposition in suckling rabbits.


METHODS
Prospective cross-over study.


METHODS
6 lactating New Zeland White rabbits and their offspring (16 days after parturition).


METHODS
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.
Aramayona
J J
JJ
Department of Pharmacology and Physiology, Faculty of Veterinary, University of Zaragoza, Spain.
Mora
J
J
Fraile
L J
LJ
García
M A
MA
Abadía
A R
AR
Bregante
M A
MA
D000818:Animals; D000831:Animals, Newborn; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D000077422:Enrofloxacin; D005260:Female; D024841:Fluoroquinolones; D007700:Kinetics; D007774:Lactation; D008657:Metabolic Clearance Rate; D008892:Milk / Q000737:chemistry*; D008954:Models, Biological; D011247:Pregnancy; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D012680:Sensitivity and Specificity; D014462:Ultrafiltration
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin