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

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.

Treatment of canine leishmaniosis with aminosidine at an optimized dosage regimen: a pilot open clinical trial.

Leishmaniosis due to Leishmania infantum (Syn: L. chagasi) is one of the most common diseases of dogs in Mediterranean countries and also has zoonotic potential. The aim of this study was to evaluate the efficacy of an optimized dosage regimen of aminosidine for the treatment of canine leishmaniosis (CanL) in terms of clinical remission, restoration of clinicopathological abnormalities, evolution of antibody titer, lymph node and bone marrow parasitic density and of PCR-based parasitological cure. Twelve non-uremic dogs without proteinuria, presenting clinical signs of CanL were included in the study. The diagnosis was confirmed by serology, microscopy and PCR of lymph node and bone marrow samples. Aminosidine was administered subcutaneously at the dose of 15 mg/kg body weight, once daily, for 21 consecutive days. A partial remission of the clinical signs, amelioration of clinicopathological abnormalities such as anemia, lymphopenia, hyperproteinemia, hyperglobulinemia, and reduced albumin/globulin ratio and reduced lymph node and bone marrow parasitic density were witnessed, although parasitological cure was not achieved. Since data are not supportive enough for the use of aminosidine as an alternative treatment, a large-scale controlled clinical trial using this optimized dosage regimen of aminosidine is warranted to compare efficacy against currently used drugs.

A cross-sectional sero-epidemiological study of canine leishmaniasis in Greek mainland.

Canine leishmaniasis is endemic in Greece as in other countries of the Mediterranean basin. In this study, the regional prevalence of canine seropositivity to Leishmania spp. in Greek mainland was simultaneously assessed in 7 different regions. A total of 2620 serum samples were collected from clinically healthy dogs and were tested for anti-L. infantum antibodies by indirect immunofluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA). A high degree of agreement (κ=0.96) was observed between these two tests. The seroprevalence rate in the whole study population was nearly 20%, being highest among dogs living in Attiki (30.12%) and lowest for those living in Florina (2.05%). There was no difference in terms of the gender of the dogs, their length of hair coat or their utility; on the contrary, seroprevalence rates were significantly higher among dogs in the age groups of 1-3 years (23.39%) and 3-9 years (23.35%) than in younger (2.26%) or older (6.03%) dogs. Epidemiological data on the seroprevalence of canine leishmaniasis provide indirect information on the prevalence of the infection and the disease and are necessary to implement and then to evaluate the effectiveness of control measures.