Pharmacokinetics of isepamicin following a single administration by intravenous infusion or intramuscular injections.

The pharmacokinetics of isepamicin following administration of a 1-g dose were evaluated for 18 healthy male volunteers between the ages of 26 and 38. In a randomized crossover fashion, each volunteer received doses of isepamicin by a 30-min intravenous infusion and as an intramuscular injection. Blood samples were collected at specified times after dosing and assayed for isepamicin by a validated radioimmunoassay method. The individual plasma concentration-time curves were analyzed by noncompartmental methods. In general, the pharmacokinetics after intravenous infusion and intramuscular injection were similar. As expected, the maximum concentration of isepamicin in serum following intramuscular injection (37.2 microg/ml) was lower than the observed concentration at the end of infusion (66.7 microg/ml). The areas under the concentration-time curves from 0 h to infinity following intramuscular and intravenous administration were 164.8 and 154.5 microg x hr/ml, respectively, indicating complete absorption following intramuscular administration. The respective mean terminal-phase half-life (t1/2) values were 2.6 and 3.6 h. Although t1/2 was slightly longer following intravenous infusion, the small difference in the observed t1/2 values was not considered to be clinically significant. Total body clearances following intramuscular injection and intravenous infusion were 1.3 and 1.4 ml/min/kg, respectively, which were similar to renal serum creatinine clearances in healthy volunteers (> 1.14 ml/min/kg). The drug was safe and well tolerated. The results of the present study clearly show complete absorption of isepamicin following intramuscular administration. The similarity in the pharmacokinetics after intravenous infusion and intramuscular dosing would permit interchangeable administration of isepamicin by either route without compromising clinical efficacy.