Pharmacokinetics and tolerability of aminosidine after repeated administrations using an optimal dose regimen in healthy dogs and in dogs with leishmaniosis

Abstract

Optimisation of dose schedules of aminoglycosides is required in order to increase efficacy and prevent their toxicity. The objective of this study was to determine the pharmacokinetic profile and the safety of aminosidine in dogs with naturally occurring leishmaniosis and in healthy dogs after once daily administration. Six young-adult, male, healthy, Beagle dogs and 12 dogs with clinical signs of canine leishmaniosis without azotemia and proteinuria were included in the study. Diagnosis of the disease was confirmed by serology, parasitology and molecular techniques. Pharmacokinetics and evaluation of renal function after repeated (once daily for 21 consecutive days) subcutaneous administration of aminosidine, at the dose of 15mg/kg b.w. in both the healthy and the diseased animals were compared. Concentrations of aminosidine were determined by high-performance liquid chromatography and pharmacokinetic analysis was performed by the non-compartmental method. No significant differences were observed between healthy and diseased dogs considering all pharmacokinetic parameters. In general, mean Cmax ranged between 46.41 and 54.32μg/mL and between 38.69 and 40.73μg/mL in healthy dogs and in dogs with canine leishmaniosis, respectively. No accumulation of the drug was observed in either group since total elimination of aminosidine and half-life lambda z were not modified throughout the administration period. Aminosidine was well tolerated in all dogs with no clinical and clinicopathological signs of nephrotoxicity. Once daily administration of high dose of aminoglycosides, resulted in effective serum concentrations and absence of nephrotoxicity.