Angiotensin II type 1 receptor blockade with 80 and 160 mg valsartan in healthy, normotensive subjects

Background: An 80-mg dose once or twice daily is the dose of valsartan frequently administered for treatment of hypertension. The target dose selected for the Val-HeFT trial in patients with chronic heart failure is 160 mg twice daily. The level and time course of angiotensin II type 1 (AT₁)-receptor blockade achieved by 160 mg valsartan have not been reported. Methods and Results: Seven normotensive healthy subjects were assigned in random order to receive a single dose of placebo, 80 mg valsartan, and 160 mg valsartan at 7- to 10-day intervals. AT₁-receptor blockade level (%) was determined by the pressure response to administration of exogenous angiotensin II. The pressure response to angiotensin II was measured at baseline and 2, 6, 12, and 24 hours after oral administration of placebo, 80 mg valsartan, and 160 mg valsartan. Eighty and 160 mg valsartan resulted in a significant and similar level of AT₁-receptor blockade at 2 and 6 hours compared with placebo. The 160-mg dose resulted in a significantly greater level of AT₁-receptor blockade than 80 mg at 12 and 24 hours. Conclusions: During the first 6 hours after oral administration of 80 and 160 mg valsartan the level of AT₁-receptor blockade is similar. However, only 160 mg valsartan provides sustained AT₁-receptor blockade over 24 hours.