Premium
Pharmacokinetics and Pharmacodynamics of Drospirenone‐Estradiol Combination Hormone Therapy Product Coadministered With Hydrochlorothiazide in Hypertensive Postmenopausal Women
Author(s) -
Karara Adel H.,
Hanes Vladimir,
Alonso Alberto,
Ni Pingping,
Poola Nagaraju,
Silang Rose,
Blode Hartmut,
Preston Richard A.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007306560
Subject(s) - drospirenone , hydrochlorothiazide , pharmacokinetics , pharmacodynamics , medicine , pharmacology , postmenopausal women , blood pressure
The effects of combination hormone therapy of drospirenone (DRSP), a novel progestin with antialdosterone properties, and 17β‐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.