Simultaneous analysis of the serum and urinary pharmacokinetics of fortimicin A after intravenous administration to healthy subjects.
The present study was conducted to evaluate the single-dose pharmacokinetics of the pseudodisaccharide antibiotic, fortimicin A, in humans, following intravenous infusion of 2.5, 5.0, and 7.5 mg per kg doses of the free base (as fortimicin A sulfate) to 17 volunteers who were randomly assigned to each of three dose groups containing six, six, and five subjects, respectively. Each dose was infused in 100 ml of 5% glucose/water over 57-63 min (i.e., an infusion rate of approximately 1.7 ml per min). Serum samples were obtained at 0, 1, 1.25, 1.5, 1.75, 2, 3, 5, 6, 8, and 12 h after the start of the infusion. Urine was collected in 0-4, 4-8, 8-12, and 12-24 h fractions (also relative to start of infusion). Determinations of fortimicin A concentrations were performed microbiologically on urine samples, and with a unique immunologic procedure on serum samples. Serum concentration-time and cumulative urinary excretion-time data for each subject were simultaneously fit to a two-compartment open model with zero-order absorption (i.e., infusion) and biexponential elimination. Of the six pharmacokinetic parameters studied (K21, K12, KNet, V1, cumulative fraction of drug excreted to infinite time, and renal clearance), significant (p = 0.05) dose-related differences were found only in the mean renal clearances between the 2.5 mg/kg dose group and the other two; however, this was of questionable practical importance. The overall mean beta-phase half-live was about 1.8 h, with little subject-to-subject variability.
D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000652:urine; D000900:Anti-Bacterial Agents; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C023384:fortimicin A