Triexponential disposition pharmacokinetics of gentamicin in rabbits.

Using a sensitive high-pressure liquid chromatographic method for the determination of gentamicin, plasma-level profiles of gentamicin were found to fit to a triexponential equation in 3 out of 4 rabbits studied after bolus intravenous administration by the application of the Minimum Akaike's Information Criterion Estimation (MAICE) method. This is different from the monoexponential or biexponential decay of gentamicin often reported in humans. Volumes of distribution of central compartment and at the steady-state in rabbits were similar to those reported in humans. Extensive distribution and tissue binding of gentamicin in rabbits were indicated by their high Vdarea, about 3.9 l/kg. It is proposed that rabbits may serve as a useful model for studying the mechanism and prediction of renal toxicity of gentamicin in patients.