Pharmacokinetics and pharmacodynamics of drospirenone-estradiol combination hormone therapy product coadministered with hydrochlorothiazide in hypertensive postmenopausal women

Adel H. Karara, Vladimir Hanes, Alberto Alonso, Pingping Ni, Nagaraju Poola, Rose Silang, Hartmut Blode, Richard A. Preston

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 post-menopausal women.

Original languageEnglish (US)
Pages (from-to)1292-1302
Number of pages11
JournalJournal of Clinical Pharmacology
Volume47
Issue number10
DOIs
StatePublished - Oct 1 2007

Keywords

  • Aldosterone
  • Aldosterone antagonists
  • Diuretics
  • Drospirenone
  • Drug interactions
  • Estradiol
  • Hormone therapy
  • Hydrochlorothiazide
  • Hypertension
  • Potassium
  • Progesterone
  • Progestogens

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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