PHARMACOKINETICS AND METABOLISM OF C-14 ISEPAMICIN IN HUMANS FOLLOWING INTRAVENOUS ADMINISTRATION

Twelve healthy adult male volunteers received Ig (base equivalent) of C-14-isepamicin (131 mu Ci) as an intravenous bolus over 5 min. The areas under the plasma concentration-time curves at infinity for isepamicin (196 mu g . h/ml) and total radioactivity (164 mu g . 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 alpha, beta, and gamma phases, respectively. However, the contribution of the gamma 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.