Abstract
Angiotensin II receptor blockers (ARBs) are effective and well-tolerated orally active
anti-hypertensive agents. The purpose of this study was to investigate the pharmacokinetic
properties of typical ARBs in the dog. 60 beagles were administered a single oral
dose of Micardis® 80 mg (telmisartan), Cozaar® 50 mg (losartan), or Diovan® 80- and 160-mg (valsartan). The plasma concentrations of these ARBs were measured
using liquid chromatography/tandem mass spectrometry and their pharmacokinetic properties
were analyzed using both non-compartmental and compartmental approaches. The half-life
and volume of distribution in dogs were in the order losartan>valsartan>telmisartan
after oral administration. Systemic exposure was estimated by calculating the area
under the plasma concentration-vs.-time curve from time zero to infinity (AUC
inf
), and resulted in the order telmisartan>valsartan>losartan. The values of C
max and AUC increased in proportion to the dose of valsartan. In compartmental analysis, the
pharmacokinetics of telmisartan and losartan pharmacokinetics fit a 2-compartment
model, while valsartan fit a 1-compartment model. These results provide detailed pharmacokinetic
information of ARBs in the dog, and may aid in future development of improved formulations
or fixed-dose combinations.
Key words
telmisartan - losartan - valsartan - pharmacokinetics - dog
