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.
Dionisotti
S
S
Research Laboratories, Schering-Plough S.p.A., Comazzo, Milan, Italy.
Bamonte
F
F
Leung
P
P
Kramer
W G
WG
Ongini
E
E
D000583:Amikacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D006168:Guinea Pigs; D006207:Half-Life; D007273:Injections, Intramuscular; D008297:Male; D009428:Netilmicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation; D013997:Time Factors
D009428:Netilmicin; D000583:Amikacin