Multiple-dose, safety, pharmacokinetics, and pharmacodynamics of a new selective estrogen receptor modulator, ERA-923, in healthy postmenopausal women.

Abstract

ERA-923 is a new selective estrogen receptor modulator under clinical investigation for use in tamoxifen refractory metastatic breast cancer. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-daily oral ERA-923 (10-200 mg) for 28 days in healthy postmenopausal females. ERA-923 was well tolerated, and adverse events were mild and reversible. No clinically significant changes in laboratory values were found with ERA-923 versus placebo. ERA-923 appeared to undergo extensive metabolism and enterohepatic recirculation. In addition, pharmacokinetic analysis showed that a high-fat breakfast increased the extent of absorption. ERA-923-dosed subjects had no uterine or ovarian changes when evaluated with transvaginal ultrasound and compared to placebo subjects. Overall, ERA-923 was safe and well tolerated in postmenopausal women dosed for 28 days.

• Authors: Monette M Cotreau, Lucille Stonis, Kevin H Dykstra, Thimma Gandhi, Maria Gutierrez, Jing Xu, Young Park, Peter H Burghart, Ullrich S Schwertschlag
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 42 Issue 2 Pg. 157-65 (Feb 2002) ISSN: 0091-2700 [Print] England
• PMID: 11831538 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• 2-(4-hydroxyphenyl)-3-methyl-1-(4-(2-piperidin-1-yl-ethoxy)-benzyl)-1H-indol-5-ol
• Biomarkers
• Indoles
• Lipids
• Piperidines
• Selective Estrogen Receptor Modulators

Topics

• Aged
• Area Under Curve
• Biomarkers
• Bone and Bones (metabolism)
• Cohort Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Fasting (physiology)
• Female
• Half-Life
• Humans
• Indoles (adverse effects, pharmacokinetics, pharmacology)
• Lipids (blood)
• Middle Aged
• Piperidines (adverse effects, pharmacokinetics, pharmacology)
• Postmenopause (physiology)
• Selective Estrogen Receptor Modulators (adverse effects, pharmacokinetics, pharmacology)