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The pharmacokinetics of isepamicin, a broad-spectrum aminoglycoside antibiotic, was studied in man after intramuscular administration. Two groups each of 6 volunteers received isepamicin for 10 consecutive days by intramuscular injection at respective doses of 7.5 mg/kg once daily or 7.5 mg/kg twice daily. Plasma and urinary concentrations of isepamicin were determined using a specific HPLC method. In both groups, there was no drug accumulation following multiple administration. The t_½, which ranged from 2.4 to 2.7 h, was independent of the dosage regimen. Isepamicin excreted into (0-24 h) urine accounted for virtually 100% of the dose. The results show that the pharmacokinetics of isepamicin are similar with these dosage regimens. The drug undergoes no detectable biotransformation, does not accumulate upon multiple dosing, and is cleared solely by urinary excretion.

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Twelve healthy adult male volunteers received 1 g (base equivalent) of 14 C-isepamicin (131 Ci) as an intravenous bolus over 5 min. The areas under the plasma concentration-time curves at infinity for isepamicin (196 g ⅐ h/ml) and total radioactivity (164 g ⅐ h/ml) were similar, indicating no biotransformation of isepamicin. The disappearance of isepamicin from plasma followed a triexponential decline, with half-lives of 0.17, 2.12, and 34 h for the ␣, ␤, and ␥ phases, respectively. However, the contribution of the ␥ phase to the total area under the concentration-time curve was only 2.6%. There were no detectable metabolites in plasma and urine, confirming that isepamicin was not biotransformed. The cumulative levels of isepamicin and total radioactivity excretion in urine from 0 to 120 h were 97.3 and 92.1% of the dose, respectively, indicating that the drug was excreted mainly as unchanged isepamicin in urine.Isepamicin is a new aminoglycoside antibiotic that has been shown to be active against bacteria that have developed resistance to other aminoglycosides (1,7,8,17). The development of resistance to this class of antibiotics has been attributed to the presence of aminoglycoside-inactivating enzymes (10,13,15).Isepamicin has been shown to be superior to other available aminoglycosides for use against resistant bacteria (5,16,19). It is more active than amikacin against clinical isolates of Escherichia coli and Citrobacter, Klebsiella, Enterobacter, and Serratia spp., which do not possess aminoglycoside-inactivating enzymes. Its activity is comparable to that of amikacin against Proteus sp. and Pseudomonas aeruginosa, which lack aminoglycoside-inactivating enzymes (6, 11). This study was conducted to evaluate the pharmacokinetics, metabolism, and excretion of 14 C-isepamicin administered intravenously to healthy adults. MATERIALS AND METHODSCompound. The 14 C-isepamicin solution used for intravenous injection (250 mg/ml) was supplied by Schering-Plough Research Institute. The 14 C-isepamicin used had a specific activity of 0.131 Ci/mg and a radiochemical purity of Ͼ99% (based on high-pressure liquid chromatography [HPLC] and liquid scintillation radiometry). The chemical identity of the compound was confirmed by mass spectrometry and nuclear magnetic resonance techniques.Drug administration. Twelve healthy male volunteers between the ages of 19 and 40 years with body weights ranging from 147 to 210 lb (ca. 67 to 95 kg) participated in this study. All volunteers were determined to be in good health through medical history, physical examination, electrocardiogram, and laboratory tests. Each subject signed an informed consent form prior to participation.All volunteers were confined to the study area for 12 h prior to the start of the study and until day 5. Ten hours prior to drug administration, a light snack was served and then an overnight fast was observed. On the morning following the fast, 4 ml of the 14 C-isepamicin solution (250 mg/ml) was administered as an intravenous bolus over 5 min for a total dose...