Concurrent Use of Tasipimidine Oral Solution and Fluoxetine in Dogs

This exploratory randomized crossover study investigated pharmacokinetic interactions, functional alertness, and cardiovascular safety of tasipimidine oral solution administered alone and in combination with fluoxetine in healthy Beagle dogs (n = 8; 4 dogs per dose level), with a 7-day washout between phases. Dogs received single oral doses of tasipimidine (20 or 30 μg/kg) alone and following single or repeated fluoxetine administration (~1 mg/kg/day for 12 days). Functional alertness was assessed using a semi-quantitative, observer-based scale evaluating responsiveness and ability to walk. Cardiovascular effects were monitored by telemetry, including heart rate, blood pressure, and ECG. Co-administration with fluoxetine increased tasipimidine exposure, with Cmax and AUC_0-24h rising approximately 1.3-1.4-fold after single fluoxetine dosing and up to 1.4-fold at the 30 μg/kg tasipimidine dose after repeated fluoxetine administration; these changes were variable and not consistently statistically significant. Reduced alertness and transient mild ataxia were more frequent at 30 μg/kg, whereas the 20 μg/kg dose showed minimal sedative effects. Tasipimidine reduced heart rate by 30-52 bpm and mean arterial pressure by 13-21 mmHg. No clinically relevant ECG abnormalities were detected. The increased tasipimidine exposure is likely related to metabolic inhibition by fluoxetine. Overall, concurrent use was well tolerated, supporting a reduced tasipimidine dose (20 μg/kg) when combined with fluoxetine.