A dose-ranging study of gentamicin pharmacokinetics: Implications for extended interval aminoglycoside therapy

Prolonged distribution time has been noted for high-dose (7 mg/kg) gentamic in. High er doses are used for extended-interval aminoglycoside therapy (EI A). The authors investigated whether the increase in distribution time was proportional to the dose of gentamicin. Twelve healthy volunteers were give n low (LD, 2 mg/kg), medium (MD, 4.5 mg/kg), and high (HD, 7 mg/kg) doses o f gentamicin in a randomized, crossover fashion. Gentamicin was infused ove r 30 minutes, with 15 concentrations obtained over 8 hours after each dose. Data were fit to a two-compartment pharmacokinetic model. Distribution hal f-life for HD (31.1 +/- 5.7 min) differed significantly (p < 0.05) from LD (22.4 +/- 6.1 min) and MD (23.8 +/- 5.1 min) with no significant difference being seen between LD and MD. This study verifies that when using EIA dosi ng with HD gentamicin, sampling within 90 minutes after the beginning of th e infusion provides information that leads to overestimation of peak serum concentration/minimum inhibitory concentration and inaccurate calculation o f pharmacokinetic parameters. <(c)> 2001 the American College of Clinical P harmacology.