Single-dose pharmacokinetics of 3-O-demethylfortimicin A in humans after intravenous and intramuscular administration.
The pharmacokinetics of 3-O-demethylfortimicin A were evaluated in 16 healthy adult male volunteers after bolus intramuscular (i.m.) and 30-min intravenous (i.v.) infusion administration of doses ranging from 0.25 to 16 mg/kg. Mean calculated peak levels of the drug in plasma after the 0.25-, 0.5-, 1-, 2-, 4-, 8-, and 16-mg/kg i.m. doses were 1.1, 1.9, 3.5, 4.9, 11.0, 21.8, and 41.3 micrograms/ml, respectively, occurring about 60 min after dosing. The biphasic decline in levels of the drug in plasma after i.v. administration was not apparent after i.m. dosing, presumably because absorption of the drug from the injection site obscured the alpha elimination phase. Mean calculated peak levels for the 1-, 2-, 4-, 8-, and 16-mg/kg 30-min i.v. infusions were 5.9, 12.2, 20.1, 36.7, and 66.4 micrograms/ml, respectively. A statistically significant trend of increasing apparent volume of distribution with increasing dose size was noted for the i.m. dose group only. Plasma drug clearance was dose level and route independent, with an excellent linear relationship between the area under the plasma drug level curve and the dose. The mean 0- to 48-h urinary recoveries of 3-O-demethylfortimicin A after the i.m. injections and i.v. infusions were 90 and 102%, respectively. After the i.m. dosings, the half-life of the drug in plasma averaged 2.0 h, and after the i.v. dosings it averaged 2.7 h. The results of the study indicated that most of the drug was cleared by renal mechanisms.
D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C027445:3-O-demethylfortimicin A