Bioavailability in the rabbit of penicillin and dihydrostreptomycin from three commercial penicillin/aminoglycoside fixed combination products for intramuscular injection.
The bioavailability of penicillin and dihydrostreptomycin from three penicillin/ aminoglycoside fixed combination products for intramuscular injection was investigated in a four-way, randomized, crossover experiment in rabbits. Attention is focused on bioequivalence based on plasma concentration vs. time profiles to study whether the rabbit is a good model to detect differences in in vivo delivery of penicillin and/or dihydrostreptomycin after intramuscular administration of different products. In all products, penicillin was present as a suspension. Although the extent of absorption of penicillin did not differ between the three products, large differences in the rates of absorption were observed. With respect to dihydrostreptomycin, no significant differences were observed between the products. The results from this study demonstrate that the rabbit is a good model to detect differences in bioavailability of suspended penicillin from penicillin /dihydrostreptomycin fixed combination products for intramuscular injection. A study with the same products is presently being carried out in calves to investigate whether bioequivalence studies in rabbits could replace studies in the target animals.
Unit of Biotransformation, Pharmaco- and Toxicokinetics, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
K
K
Groen
D P
DP
Pereboom-De Fauw
A
A
Van Veen-Rutgers
A G
AG
Vulto
A J
AJ
De Neeling
D000042:Absorption; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004096:Dihydrostreptomycin Sulfate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular / Q000592:standards / Q000662:veterinary*; D007275:Injections, Intravenous / Q000662:veterinary; D010406:Penicillins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D013810:Therapeutic Equivalency
D000900:Anti-Bacterial Agents; D010406:Penicillins; D004096:Dihydrostreptomycin Sulfate