Preliminary Safety Study of the Combination Therapy of Miltefosine and Allopurinol in Dogs
C. Vischer1; D. Grousson1; C. Médaille2
Canine leishmaniosis is a zoonotic and life-threatening protozoal infection due to Leishmania infantum. The current recommended treatment is meglumine antimoniate combined with allopurinol.
Miltefosine, an alkylphosphocholine, is an oral antiprotozoal agent with in vitro and in vivo direct anti-leishmanial activity. As a leishmanicidal agent, miltefosine can be considered as an alternative treatment option, combined with allopurinol.
To confirm the safety of miltefosine and allopurinol administered in combination to healthy dogs.
The dogs were treated for 28 days with 14 days follow-up. Six healthy 6-month old beagles were divided into:
Group 1: 4 dogs administered 2mg/kg PO SID miltefosine and 10mg/kg PO BID allopurinol for 28 days.
Group 2: 2 dogs administered 2mg/kg PO SID miltefosine for 28 days (controls).
Blood samples were taken on D0, D14, D28 and D42 for CBC and biochemistry. Dogs were observed daily and full clinical examinations were performed weekly.
The animals remained in good health throughout the trial. An equivalent and normal weight evolution was seen in both groups. Blood results remained unchanged throughout the treatment and follow-up.
In group 1, minor bile-tinged vomit (3 dogs on D12, D13 and D15 respectively) and lose faeces (2 dogs on D15 and D26 respectively) were observed. These were self-limiting and no biochemistry changes were detected.
The combination of miltefosine (2mg/kg SID) and allopurinol (10mg/kg BID) for 28 days was demonstrated to be safe. This is being confirmed by a multi-centric controlled clinical field trial.