Pharmacokinetics of intravenously administered isepamicin in men

The pharmacokinetics of isepamicin, a broad-spectrum aminoglycoside antibiotic, were studied in men after intravenous administration. Three groups of six volunteers received isepamicin for 10 consecutive days by 0.5-h intravenous infusions at respective dosages of 7.5 mg/kg of body weight once daily, 7.5 mg/kg twice daily, and 15 mg/kg once daily. Levels of isepamicin in plasma and urine were determined by a specific high-performance liquid chromatography method. For all three groups, steady-state concentrations of the drug in plasma were attained with the first dose. The area under the concentration-time curve for plasma and urinary drug excretion were dose proportional. A half-life ranging from 2.0 to 2.5 h was independent of the dosage regimen. Isepamicin excreted in urine over 24 h accounted for about 100% of the dose. The results show that the pharmacokinetics of isepamicin are linear with these dosage regimens. The drug does not accumulate upon multiple dosing, undergoes no detectable biotransformation, and is cleared solely by urinary excretion.