Pharmacokinetics and pharmacodynamics (PK/PD) of irbesartan in Beagle dogs after oral administration at two dose rates

Abstract

Irbesartan (Irb) is an angiotensin II type 1 receptor antagonist widely used in humans to treat hypertension. Age-related diseases such as hypertension are increasingly being diagnosed in dogs and there is the need for new drugs. The PK/PD of Irb was tested in Beagle dogs. Ten healthy Beagles were orally administered two dose rates (2 and 5 mg/kg), according to a cross over study design. Blood collections for PK analysis and systolic blood pressure (SBP), heart and respiratory rate, mucous membranes colour, capillary refill time and temperature evaluations were performed at scheduled intervals. The drug plasma concentration was dose dependent. The dogs administered 5 mg/kg showed a significant reduction in SBP, while in those receiving 2 mg/kg, this parameter was minimally affected. A counter clockwise hysteresis showed no direct correlation between SBP and plasma concentrations. The minimum effective concentration was theorized to be within the range 550-800 ng/mL. Although further studies are necessary, 5 mg/kg seems to be the more appropriate dose to obtain a hypotensive effect in Beagle dogs.

Attenuation of the pressor response to exogenous angiotensin by angiotensin receptor blockers and benazepril hydrochloride in clinically normal cats

“…9 Although similar data for losartan or irbesartan in this species are not available, data on dogs suggest that losartan's parent compound has a mean ± SEM Tmax of 0.86 ± 0.67 hours and irbesartan has a Tmax of 2.83 ± 0.31 hours to 5.52 ± 2.33 hours. 22 Although testing cats at the 90-minute posttreatment time point was intended to approximate the time of peak effect of each drug, it is possible that differences in performance among these drugs may be attributed to differences in the timing of maximum drug effect.…”