J Clin Pharmacol
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Karara, A. H.
Right arrow Articles by Preston, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Karara, A. H.
Right arrow Articles by Preston, R. A.

PHARMACOKINETICS AND PHARMACODYNAMICS

Pharmacokinetics and Pharmacodynamics of Drospirenone-Estradiol Combination Hormone Therapy Product Coadministered With Hydrochlorothiazide in Hypertensive Postmenopausal Women

Adel H. Karara, PhD, FCP, Vladimir Hanes, MD, Alberto Alonso, MD, PA, Pingping Ni, PhD, Nagaraju Poola, PhD, Rose Silang, BS, Hartmut Blode, PhD and Richard A. Preston, MD, MSPH

From Berlex Pharmaceuticals, Inc, Montville, New Jersey (Dr Karara, Dr Hanes, Dr Ni, Dr Poola, Ms Silang); Division of Clinical Pharmacology and Pharmacokinetics Clinical Research Center, Department of Medicine, Miller School of Medicine, University of Miami, Florida (Dr Alonso, Dr Preston); and Bayer Schering Pharma AG, Clinical Pharmacokinetics, Berlin, Germany (Dr Blode).

The effects of combination hormone therapy of drospirenone (DRSP), a novel progestin with antialdosterone properties, and 17ß-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.

Key Words: Hormone therapy • hypertension • estradiol • drospirenone • aldosterone • aldosterone antagonists • progesterone • progestogens • hydrochlorothiazide • potassium • diuretics • drug interactions

Address for correspondence: Dr. A. Karara, Clinical Pharmacology at Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110-1199.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American College of Clinical Pharmacology