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 (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.
Andrawis
N S
NS
Department of Medicine and Pharmacology, Georgetown University Medical Center, Washington, D.C., USA.
Battle
M M
MM
Klamerus
K J
KJ
Burghart
P H
PH
Neefe
L
L
Weinryb
I
I
Mayer
P
P
Abernethy
D R
DR
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D001262:Atenolol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016037:Single-Blind Method; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D011743:Pyrimidines; D013777:Tetrazoles; D000804:Angiotensin II; C086167:tasosartan; D001262:Atenolol