In canine leishmaniosis (CanL), kidneys are affected in virtually all dogs. Treatment of CanL is limited in Europe to meglumine antimoniate and miltefosine. This study evaluated the pharmacological, toxicological, and pathological effects of both drugs in healthy beagle dogs. Four male and four female dogs were divided into two groups. The animals in Group 1 were administered an oral solution of 2% of miltefosine at 2 mg/kg b.w. once a day, for twenty-eight days. The animals in Group 2 were administered a preparation of meglumine antimoniate at 100 mg/kg b.w. subcutaneously once a day for twenty-eight days. After treatment, all dogs were followed-up for a further twenty-eight days. Dogs were observed daily and clinically examined ten times throughout the study. On days -1 and 55 a renal biopsy was performed on all dogs and analyzed by light microscopy, immunofluorescence, and electron microscopy. All the examinations failed to demonstrate any lesions in the miltefosine-treated dogs. Conversely, all the meglumine antimoniate-treated dogs demonstrated severe tubular damage, characterized by tubular cell necrosis and apoptosis. In conclusion, although no clinical signs of renal disease were evident, the use of meglumine antimoniate in the pharmacological treatment approach of CanLaffected dogs should be carefully considered.
The aim of this trial was to evaluate the effectiveness and safety of miltefosine-allopurinol combination therapy vs. the current reference combination therapy, meglumine antimoniate-allopurinol, for canine leishmaniosis. Dogs included in the study exhibited clinical signs of the disease, were positive by PCR and serologically positive by immunofluorescent antibody test for leishmaniosis, and negative for ehrlichiosis. Dogs were divided into two groups: Group 1 was treated with 2 mg ⁄ kg of miltefosine orally once daily for 28 days and 10 mg ⁄ kg of allopurinol orally twice daily for 7 months; Group 2 was treated with 50 mg ⁄ kg of meglumine antimoniate sub-cutaneously twice daily for 28 days and allopurinol (same dose as Group 1) for 7 months. Dogs were examined according to the following schedule: pre-inclusion, Day 0 (D0), D14, D28, D84, D140 and D196. At each visit, blood, urine and bone marrow samples were collected. Parameters monitored included haematology, biochemistry, protein electrophoresis, serology, urinary protein ⁄ creatinine ratio and RTQ-PCR performed on bone marrow aspirates. A significant reduction in total clinical score and parasite load was observed in both groups over the 7-month study period (P < 0.0001), with no significant difference between groups (P = 0.3). The safety of miltefosineallopurinol combination therapy was confirmed by lack of effect on renal and hepatic parameters and adverse reactions. Miltefosine, in combination with allopurinol, offers a safe, convenient and effective alternative treatment option for canine leishmaniosis compared to the reference therapy.
The aim of this study was to compare the efficacy and safety of oral administration of miltefosine (Milteforan) at 2 mg/kg/day for 28 days (Group M; n = 60) with a subcutaneous administration of meglumine antimoniate (Glucantime) at 50 mg/kg/12 h or at 100 mg/kg/day for 28 days (Group G; n = 59) in the treatment of canine leishmaniosis in dogs. Out of 119 dogs included in the study, 90 could be used for efficacy assessment and 112 for safety assessment. Treated dogs were followed up for 6 weeks, with re-checks every 14 days. The mean total clinical scores significantly decreased throughout the study in both treatment groups. The evolution of parasitological results after treatment (D42) shows a high percentage of dogs with negative bone marrow smears, 90% and 91.3% in groups M and G respectively, and did not significantly differ between groups (p = 0.8066). Out of the 112 dogs used for the safety assessment, only 26 dogs (23.2%) presented product-related adverse events concerning the gastrointestinal tract. These results showed that miltefosine at 2 mg/kg once daily can be safely used over a 28-day period in the treatment of canine leishmaniosis and provides both a steadily increasing improvement of the clinical signs and a good leishmanicidal efficacy.
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