The primary objective of this study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of
tasosartan and
atenolol administered alone and concomitantly under steady-state conditions in 17 patients ages 18 to 65 years diagnosed with stage 1 to 2
essential hypertension. After a 3- to 14-day qualification period, all patients received placebo
tasosartan on days--1 through 5 and 25 through 34,
atenolol alone (50 mg) on days 1 through 5,
atenolol (50 mg) +
tasosartan (50 mg) on days 6 through 19, and
tasosartan (50 mg) alone on days 20 through 24. A PK and PD evaluation of
atenolol alone was performed on study day 5. On study day 19, PK and PD of both
tasosartan and
atenolol were assessed. PK and PD evaluation for
tasosartan alone was assessed on study day 24. The coadministration of
atenolol +
tasosartan did not affect the pharmacokinetics of
tasosartan, its major metabolite (
enoltasosartan), or
atenolol when compared with
tasosartan or
atenolol administered separately. For area under the change in diastolic blood pressure curve, the reduction was significantly greater after
tasosartan +
atenolol compared with that after
atenolol alone (336 +/- 85 and 190 +/- 71 mmHg.24 h; p < 0.05 for combination and
atenolol alone, respectively; mean +/- SEM). Combination
therapy also caused a maximal reduction in diastolic blood pressure that is significantly more than with monotherapy with
atenolol (-27 +/- 2 mmHg and -20 +/- 2 mmHg, respectively, p < 0.05). The additive effects of
tasosartan and
atenolol in decreasing diastolic blood pressure may provide a rationale for combination
antihypertensive therapy.