Limited capacity of neonatal rabbits to eliminate enrofloxacin and ciprofloxacin.
The pharmacokinetics of enrofloxacin (ENR) and ciprofloxacin (CIP) in newborn and young rabbits were studied. Rabbits of different ages (1-, 8-, 16-, and 30-day-old) were administered, by the intraperitoneal route (i.p.), a dose of 7.5 mg of either drug/kg. In 1-, 8-, and 16-day-old rabbits, blood samples were drawn by cardiac puncture, under light ether anaesthesia, at predetermined times after drug administration. In 30-day-old rabbits, serial blood samples were drawn through an arterial catheter. Plasma was immediately obtained and analysed using an HPLC method. ENR and CIP plasma protein binding was also determined. The plasma pharmacokinetic profiles of ENR and CIP obtained for 30-day-old rabbits agreed with those reported in the literature for healthy adult rabbits. Nevertheless, significant differences were observed for the body clearance, the slope of the terminal phase, the volume of distribution, and the area under the curve when compared with those for younger animals (1-, 8-, and 16-day-old rabbits), indicating a limited capacity of neonatal rabbits to eliminate ENR and CIP. No differences were found when we compared the calculated values for ENR or CIP plasma protein binding as a function of the postnatal age, indicating that development does not seem to alter the free fraction of these drugs in the rabbit. Taking into account that extensive placental and milk transfer has been reported for these drugs after administration to pregnant or nursing rabbits, a cautious, attitude regarding their use in these animals must be adopted.
Fraile
L J
LJ
Department of Pharmacology and Physiology, Faculty of Veterinary, University of Zaragoza, Spain.
Martinez
C
C
Aramayona
J J
JJ
Abadía
A R
AR
Bregante
M A
MA
García
M A
MA
D000375:Aging / Q000097:blood / Q000378:metabolism / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D000833:Animals, Suckling / Q000097:blood / Q000378:metabolism / Q000502:physiology; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077422:Enrofloxacin; D005260:Female; D024841:Fluoroquinolones; D007274:Injections, Intraperitoneal / Q000379:methods / Q000662:veterinary; D008297:Male; D008954:Models, Biological; D011485:Protein Binding; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D011897:Random Allocation
D000890:Anti-Infective Agents; D001798:Blood Proteins; D024841:Fluoroquinolones; D015363:Quinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin