A pharmacokinetic and pharmacodynamic study of the potential drug interaction between tasosartan and atenolol in patients with stage 1 and 2 essential hypertension

The primary objective of this study was to evaluate the pharmacokinetics (P K) and pharmacodynamics (PD) of tasosartan and atenolol administered alone and concomitantly under steady-state conditions in 17 patients ages 18 to 6 5 years diagnosed with stage 2 to 2 essential hypertension. After a 3- to 1 4-day qualification period, all patients received placebo tasosartan on day s -1 through 5 and 25 through 34, atenolol alone (50 mg) on days I through 5, atenolol(50mg) + 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 al one was performed on study day 5. On study day 19, PK and PD of both tasosa rtan 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 (e noltasosartan), or atenolol when compared with tasosartan or atenolol admin istered separately For area under the change in diastolic blood pressure cu rve, the reduction was significantly greater after tasosartan + atenolol co mpared 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 pre ssure 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 provi de a rationale for combination antihypertensive therapy. (C) 2000 the Ameri can College of Clinical Pharmacology.