Pharmacokinetics and antihypertensive effect of pelanserin in dogs

: Pelanserin pharmacokinetics were studied in six normotensive dogs after intravenous and oral administration. Additionally, the relationship between pelanserin plasma levels and its antihypertensive effect was studied in six hypertensive dogs after a single oral administration. Plasma level-time curves were fitted to an open two compartments model. Pelanserin bioavailability after oral dosing was about 30%, this could be due to a poor absorption from the gastrointestinal tract or to an important hepatic biotransformation by first pass effect. On the other hand, oral administration of pelanserin resulted in a significant antihypertensive effect that was not followed by tachycardia. Pelanserin plasma levels did not significantly correlate with the obtained antihypertensive effect. These results suggest that the observed effect was not only due to an action at peripheral level, but other mechanisms could likely be involved, probably with participation of the central nervous system. The pharmacokinetic and pharmacodynamic profiles of pelanserin allow to predict that this drug could have a place in the therapeutics of arterial hypertension.