[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). II. Accumulation of HAPA-B after multiple administration in rats].

The accumulation of isepamicin sulfate (HAPA-B) in tissues and plasma was studied upon multiple intramuscular and intravenous administrations of 25 mg/kg of HAPA-B daily for 8 or 15 days to male rats. Shapes of plasma concentration curves in multiple intramuscular and intravenous administrations were very similar to that in a single administration. Drug concentrations in kidney at 24 hours after 8- and 15-multiple administrations through both routes were 3 to 4 and 4 to 5 times as high as that after a single administration. The concentration in kidney increased by multiple administrations for 8 days, but did not increase so highly there after till the 15-multiple administrations. On the other hand, the elimination of HAPA-B from kidney after multiple administrations was similar to that after a single administration. The accumulation of HAPA-B upon multiple administration was also observed in lung, heart, spleen and liver, but peak concentrations of the drug in these tissues were lower than that in kidney.