BIOEQUIVALENCE STUDY IN CALVES OF 3 COMMERCIAL PENICILLIN DIHYDROSTREPTOMYCIN FIXED COMBINATION PRODUCTS FOR INTRAMUSCULAR INJECTION/

A bioequivalence study with three penicillin/dihydrostreptomycin fixed combination products for intramuscular administration was performed i n dairy caIves. In addition to plasma concentrations of penicillin and dihydrostreptomycin, creatine phosphokinase concentrations were deter mined during a period of 72 h after administration of the drug product s, Considerable differences were observed in the pharmacokinetics of p enicillin from the three products. Although the extent of absorption w as similar for all products, one product showed a significantly slower release from the site of injection. Except for the AUC, the 90% confi dence intervals for these parameters exceeded the acceptable range of 0.80-1.20, Therefore, these products are not bioequivalent with respec t to the rate of absorption of penicillin. Concerning the pharmacokine tics of dihydrostreptomycin in calves, it could not be concluded that the products were bioequivalent, since the 90% confidence intervals of the ratios for C-max, t(max) and MRT exceeded the range of 0.80-1.20. From this study in calves, it was also found that the product with th e slowest release of penicillin from the injection site caused the mos t severe tissue damage, based on plasma creatine phosphokinase concent rations. Comparing the results from this study in calves with those fr om a previous study in rabbits, it can be concluded that the rabbit is a good animal model that could substitute for large animals, at least calves, in bioequivalence studies for penicillin/dihydrostreptomycin fixed combination products.