[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). I. Absorption, distribution, metabolism and excretion in rats].

Absorption, distribution, metabolism and excretion of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, after a single administration were studied in rats. After intramuscular administration of HAPA-B at a dose level between 6.25 and 100 mg/kg, the drug was rapidly absorbed to reach the peak in 0.10 to 0.21 hour (Tmax). The maximum drug concentration in the plasma (Cmax) and the size of the area under the plasma concentration-time curve (AUC) depended on dose levels. The HAPA-B disappeared rapidly from the plasma after intramuscular and intravenous administrations with biological half-lives (T1/2) from 0.41 to 0.47 hour with intramuscular administration and from 0.23 to 0.35 hour with intravenous administration. Peak time after intramuscular, intraperitoneal and subcutaneous administration of HAPA-B at a dose of 25 mg/kg were 0.18, 0.24 and 0.37 hour, respectively. Maximum drug concentrations in plasma were 64.15, 53.71 and 40.39 micrograms/ml and biological half-lives of the drug were 0.47, 0.73 and 0.87 hour, respectively. The HAPA-B was distributed rapidly into tissues, especially at a high level into kidney after intramuscular or intravenous administration of 25 mg/kg. Concentrations in lung and heart were next to that in kidney, but were not higher than plasma concentrations. The drug was excreted mainly into the urine after intramuscular and intravenous administration within 24 hours and approximately 79 to 90% of the administered amount was excreted. Meanwhile, the excretion of HAPA-B into the bile was 0.1% or less during the first 24 hours after intramuscular and intravenous administration. Bioautograms of thin layer chromatographs of 0 approximately 6 hours urine samples after intramuscular administration showed single bands with the identical Rf value to the standard HAPA-B. No difference between male and female was observed in the fate of the administered HAPA-B through intramuscularly. The shape of the plasma concentration curve and the urinary excretion after intramuscular administration of HAPA-B at the dose of 25 mg/kg was similar to those of amikacin (AMK) and gentamicin. Tissue concentrations after intramuscular and intravenous administration of HAPA-B were also similar to AMK.