PHARMACOKINETICS AND PHARMACODYNAMICS OF IRBESARTAN IN BEAGLE DOGS AFTER ORAL ADMINISTRATION AT TWO DOSE RATES.

摘要

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