Rabbit model for estimating relative bioavailability, residues and tissue tolerance of intramuscular products: comparison of two ampicillin products.
A rabbit model for simultaneous investigation of the bioavailability, tissue residues and tissue tolerance of intramuscularly administered veterinary medicines is described. The bioavailability of ampicillin from two intramuscular products, which had been found to be different in calves, were compared in a two-way crossover design. The ampicillin levels in plasma, ampicillin residues in tissues, the plasma creatine kinase activity and the tissue damage at the injection sites were studied. The absolute bioavailabilities for the products were 100% and 40%. Differences in pharmacokinetics of ampicillin between sexes were observed after intravenous and intramuscular administration. Only slight tissue damage could be detected at the injection sites after intramuscular administration of these products. The results were compared with those obtained previously in calves and were found to be similar. Further investigations with other intramuscular drug products to validate this model are under way.
Olling
M
M
Unit Biotransformation, Pharmaco- and Toxicokinetics, Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
van Twillert
K
K
Wester
P
P
Boink
A B
AB
Rauws
A G
AG
D000667:Ampicillin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003402:Creatine Kinase / Q000097:blood; D018592:Cross-Over Studies; D004350:Drug Residues / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation; D015203:Reproducibility of Results; D012727:Sex Characteristics; D014018:Tissue Distribution
D000667:Ampicillin; D003402:Creatine Kinase