Pharmacokinetics of a single dose of fulvestrant prolonged-release intramuscular injection in postmenopausal women awaiting surgery for primary breast cancer

• Published in: Clinical therapeutics 2003-05, Vol.25 (5), p.1440-1452
• Main Authors: Robertson, John F.R., Odling-Smee, William, Holcombe, Chris, Kohlhardt, Stanley R., Harrison, Mike P.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - pharmacokinetics; Antineoplastic Agents, Hormonal - therapeutic use; Area Under Curve; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - surgery; Chemistry, Pharmaceutical; Chemotherapy; Delayed-Action Preparations; Estradiol - administration & dosage; Estradiol - analogs & derivatives; Estradiol - pharmacokinetics; Estradiol - therapeutic use; Female; Half-Life; Humans; Injections, Intramuscular; Medical sciences; Pharmacology. Drug treatments; Postmenopause; Tamoxifen - administration & dosage; Tamoxifen - pharmacokinetics; Tamoxifen - therapeutic use
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(03)80131-5

Objective: The aim of this study was to describe the pharmacokinetics of 3 different single doses of fulvestrant—a new estrogen receptor (ER) antagonist that downregulates the ER with no known agonist effects—administered as a prolonged-release IM formulation. Methods: Pharmacokinetic data were obtained in a randomized, partially blinded, placebo-controlled, parallel-group, Phase I/II multicenter trial involving postmenopausal women with primary breast cancer (clinical stages T1–T3, with tumors that were ER positive or of unknown ER status) awaiting curative-intent surgery. Patients received either IM fulvestrant (50, 125, or 250 mg), oral tamoxifen (20 mg, once daily), or oral placebo (once daily). Treatment started 2 to 3 weeks before surgery and blood was taken at various times up to 12 weeks after fulvestrant administration to assess pharmacokinetic variables. Results: A total of 200 patients entered the trial, of whom 58 took part in the pharmacokinetic analysis (50 mg, n = 20; 125 mg, n = 16; 250 mg, n = 22). Following single IM injections of fulvestrant, the median time to maximum concentration was 6.98, 6.98, and 6.96 days in the 50-, 125,- and 250-mg dose groups, respectively, with an overall range of 2 to 19 days). The plasma concentration-time profiles were primarily controlled by the rate of absorption from the injection site; post-peak plasma concentrations declined over time and were measurable up to 84 days after administration of fulvestrant 125 and 250 mg. Plasma