title: 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 15 mg/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 54.32 μg/mL and between 38.69 and 40.73 μg/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.
authors.affiliation: Clinic of Medicine, Faculty of Veterinary Medicine, University of Thessaly, Trikalon Str 224, GR-43100 Karditsa, Greece. Electronic address: lathan@vet.uth.gr.
authors.forename: L V
authors.initials: LV
authors.lastname: Athanasiou
authors.affiliation: Laboratory of Pharmacology, School of Veterinary Medicine, Aristotle University of Thessaloniki, Greece.
authors.forename: G C
authors.initials: GC
authors.lastname: Batzias
authors.affiliation: Clinic of Medicine, Faculty of Veterinary Medicine, University of Thessaly, Trikalon Str 224, GR-43100 Karditsa, Greece.
authors.forename: M N
authors.initials: MN
authors.lastname: Saridomichelakis
authors.affiliation: Laboratory of Pharmacology, School of Veterinary Medicine, Aristotle University of Thessaloniki, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Delis
authors.affiliation: Companion Animal Clinic, School of Veterinary Medicine, Aristotle University of Thessaloniki, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Soubasis
authors.affiliation: Department of Veterinary Public Health, National School of Public Health, 11513 Athens, Greece.
authors.forename: V I
authors.initials: VI
authors.lastname: Kontos
authors.affiliation: Companion Animal Clinic, School of Veterinary Medicine, Aristotle University of Thessaloniki, Greece.
authors.forename: T S
authors.initials: TS
authors.lastname: Rallis
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004283:Dog Diseases / Q000188:drug therapy* / Q000469:parasitology; D004285:Dogs; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D006207:Half-Life; D007279:Injections, Subcutaneous / Q000662:veterinary; D007891:Leishmania / Q000187:drug effects*; D007896:Leishmaniasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D008297:Male; D010303:Paromomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D010303:Paromomycin
keywords: Aminosidine; Dog; Leishmania; Nephrotoxicity; Pharmacokinetics; Tolerability