A phase I study of the pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose anastrozole in healthy, premenopausal female volunteers.
OBJECTIVE
To evaluate the pharmacokinetic, pharmacodynamic, and safety profiles of the aromatase inhibitor anastrozole in healthy, premenopausal women.


METHODS
Phase I, single-center study.


METHODS
Infertility clinic.


METHODS
Twenty-six women with regular ovulatory cycles: 20 received either a single dose of 5 mg, 10 mg, 15 mg, or 20 mg anastrozole, or remained untreated; 6 received five daily doses of 10 mg or 15 mg anastrozole.


METHODS
Anastrozole was administered on cycle day 2 for the single-dose groups and on days 2-6 for the multiple-dose groups. Ultrasound follicular development and endometrial biopsies were performed. Safety was determined from adverse event reports and laboratory parameters.


METHODS
Pharmacokinetics, pharmacodynamics, and safety.


RESULTS
The pharmacokinetics of anastrozole were linear, predictable, and consistent with previously published data in healthy volunteers. In the single-dose groups, E2 levels reached their nadir 3-6 hours after administration, decreasing by an average of 39% from baseline. Follicle-stimulating hormone levels rose by 13%, 52%, 49%, and 75% in the 5-mg, 10-mg, 15-mg, and 20-mg groups, respectively, at approximately 24 hours after dosing. Most subjects recruited just one mature follicle, with no apparent effect on endometrial maturation. No safety concerns were noted.


CONCLUSIONS
Anastrozole was well tolerated and suppressed E2 levels, with a resultant increase in FSH.
Tredway
Donald R
DR
Reproductive Health and Global Product Development Unit, Serono Inc., Rockland, Massachusetts 02370, USA. donald.tredway@serono.com
Buraglio
Mauro
M
Hemsey
George
G
Denton
Geoff
G
D000328:Adult; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004717:Endometrium / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008599:Menstruation Disturbances / Q000139:chemically induced; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006080:Ovarian Follicle / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D017697:Premenopause; D012016:Reference Values; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014463:Ultrasonography
D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D004958:Estradiol; D005640:Follicle Stimulating Hormone