[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). IV. Intramuscular, intravenous and drip intravenous administration of HAPA-B in dogs].

The plasma concentration and urinary excretion of isepamicin sulfate (HAPA-B) were studied following intramuscular, intravenous and drip intravenous administrations of 6.25, 25 and 100 mg/kg in dogs. Maximum plasma concentrations (Cmax) of HAPA-B after intramuscular, intravenous and drip intravenous administration depended on dosage levels. Biological half-lives (T1/2) and areas under plasma concentration-time curves (AUC) for the three different routes of administration were similar to each other. The peak plasma concentration of HAPA-B achieved with intramuscular administration was similar to that with a 1-hour drip intravenous administration at a dose level of 6.25 or 25 mg/kg. On the other hand, at a dose level of 100 mg/kg, the Cmax following intramuscular administration was similar to that following 2-hour drip intravenous administration. It was, therefore, presumed that the plasma concentration curves which are similar to that of intramuscular administration can be obtained by regulating the infusion time. The observed Cmax value for drip intravenous administration was a little higher than the theoretical Cmax value for drip intravenous administration calculated from parameters for intramuscular administration. Simulation curves obtained for extended infusion times agreed more closely with observed curves than curves simulated for shorter infusion periods. These investigations showed that plasma concentration curves for any dosage levels can be estimated from parameters calculated from experimental data obtained using intramuscular or drip intravenous administration. HAPA-B was rapidly excreted into the urine after administration through any of these 3 routes and 71 approximately 89% of the dose was excreted into the unrine in 24 hours at all dosage levels. Bioautograms of thin-layer chromatographs of the 0 approximately 6 hours urine after intramuscular administration showed single bands with a similar Rf value to that of the standard HAPA-B. No significant differences in plasma concentration and urinary excretion between HAPA-B and amikacin were observed upon intramuscular or intravenous administration of 25 mg/kg.