BIOAVAILABILITY IN THE RABBIT OF PENICILLIN AND DIHYDROSTREPTOMYCIN FROM 3 COMMERCIAL PENICILLIN AMINOGLYCOSIDE FIXED COMBINATION PRODUCTS FOR INTRAMUSCULAR INJECTION/

The bioavailability of penicillin and dihydrostreptomycin from three p enicillin/aminogIycoside fixed combination products for intramuscular injection was investigated in a four-way, randomized, crossover experi ment in rabbits. Attention is focused on bioequivalence based on plasm a concentration vs. time profiles to study whether the rabbit is a goo d model to detect differences in in vivo delivery of penicillin and/or dihydrostreptomycin after intramuscular administration of different p roducts. In ail products, penicillin was present as a suspension. Alth ough the extent of absorption of penicillin did not differ between the three products, large differences in the rates of absorption were obs erved, With respect to dihydrostreptomycin, no significant differences were observed between the products. The results from this study demon strate that the rabbit is a good model to detect differences in bioava ilability of suspended penicillin from penicillin/dihydrostreptomycin fixed combination products for intramuscular injection. A study with t he same products is presently being carried out in calves to investiga te whether bioequivalence studies in rabbits could replace studies in the target animals.