Concurrent Use of Tasipimidine Oral Solution and Clomipramine in Dogs

The study evaluated pharmacokinetics, effects on functional alertness, and cardiovascular parameters of tasipimidine oral solution (Tessie, Orion Corporation) alone and in combination with oral clomipramine in six healthy laboratory dogs. Pharmacokinetics and functional alertness were studied after a single dose (Phase 1) and after 4 days of repeated twice daily dosing of tasipimidine 30 μg/kg and clomipramine at approximately 1 mg/kg, alone and in combination (Phase 2). Additionally, the combination was studied with a reduced dose of tasipimidine (20 μg/kg) as single and repeated dosing (Phase 3). Alertness was slightly reduced by the combination of tasipimidine 30 μg/kg with clomipramine. Decreasing tasipimidine dose to 20 μg/kg caused less reduction in alertness. Tasipimidine alone and in combination with clomipramine was well tolerated in respect to cardiovascular effects (BP, HR, and ECG). The exposure levels of tasipimidine were similar alone and in combination with clomipramine when administered as a single dose. After repeated dosing, tasipimidine exposure was higher when combined with clomipramine. Slightly slower absorption of clomipramine was observed when dosed concomitantly with tasipimidine, but there was no significant difference in plasma exposure. Effect on functional alertness supports the use of the lower dose of tasipimidine (20 μg/kg) when combined with clomipramine 1 mg/kg.