Aminoglycoside dosing regimen and pharmacokinetic parameters in the guinea pig

To complement a study on aminoglycoside dosing regimen and ototoxicity in the guinea pig, we designed an experiment to examine: (1) the effect of dosing regimen on guinea pig pharmacokinetic parameters, and (2) possible differential accumulation after repeated intramuscular administrations of netilmicin and amikacin (150 mg/kg/day) for 7 days by 1 or 3 daily injections. The area under the curve (AUC infinity) and the maximum plasma concentration (Cmax) were dose-dependent. Within each regimen, no significant difference was observed between days 1 and 7. Little or no accumulation was observed after 21 days of treatment. The results show a good dose-dependence of AUC infinity and Cmax and are in accordance with data from human studies. Moreover, the fact that no accumulation occurred in the guinea pig suggests that it is a suitable animal model to evaluate the relation between aminoglycoside ototoxicity and dosing regimen.