Pharmacokinetics and pharmacodynamics of drospirenone-estradiol combination hormone therapy product coadministered with hydrochlorothiazide in hypertensive postmenopausal women.
The effects of combination hormone therapy of drospirenone (DRSP), a novel progestin with antialdosterone properties, and 17beta-estradiol (E2) on hydrochlorothiazide (HCTZ) pharmacokinetics/pharmacodynamics versus placebo were investigated in a double-blind, placebo-controlled, crossover study. Thirty-six postmenopausal women with stage 1 hypertension maintained on 25 mg of HCTZ once daily were randomized to receive either 3 mg of DRSP/1 mg of E2 or placebo once daily for 4 weeks. Plasma HCTZ, serum DRSP, E2, potassium, aldosterone, and plasma renin activity were determined at baseline and after 4 weeks. Results showed that the combination of DRSP/E2 plus 25 mg of HCTZ is safe and well tolerated in hypertensive postmenopausal women. The pharmacokinetics of HCTZ were not affected by coadministration of DRSP/E2. The geometric mean ratios and 90% confidence intervals ([HCTZ + DRSP/E2]/[HCTZ + placebo]) for HCTZ (a) area under the serum/plasma concentration-time curve from 0 to 24 hours and (b) maximum plasma concentration were 101 (90.7, 112) and 103 (92.8, 115), respectively. In the HCTZ + DRSP/E2 group, serum potassium, aldosterone, and plasma renin activity all increased in a manner marginally consistent with a beneficial antialdosterone effect, counteracting the HCTZ-induced potassium loss and lowering both systolic and diastolic blood pressure. No dose adjustment is required when DRSP/E2 is added to antihypertensive therapy with HCTZ in hypertensive postmenopausal women.
Karara
Adel H
AH
Berlex Pharmaceuticals Inc., Montville, New Jersey, USA.
Hanes
Vladimir
V
Alonso
Alberto
A
Ni
Pingping
P
Poola
Nagaraju
N
Silang
Rose
R
Blode
Hartmut
H
Preston
Richard A
RA
D000368:Aged; D000450:Aldosterone / Q000097:blood; D000736:Androstenes / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D017698:Postmenopause; D011188:Potassium / Q000097:blood
D000736:Androstenes; D000959:Antihypertensive Agents; D004338:Drug Combinations; D004967:Estrogens; D000451:Mineralocorticoid Receptor Antagonists; D006852:Hydrochlorothiazide; D000450:Aldosterone; D004958:Estradiol; C035144:drospirenone; D011188:Potassium