title: A phase I study of the pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose anastrozole in healthy, premenopausal female volunteers.
abstract: 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.
authors.affiliation: Reproductive Health and Global Product Development Unit, Serono Inc., Rockland, Massachusetts 02370, USA. donald.tredway@serono.com
authors.forename: Donald R
authors.initials: DR
authors.lastname: Tredway
authors.forename: Mauro
authors.initials: M
authors.lastname: Buraglio
authors.forename: George
authors.initials: G
authors.lastname: Hemsey
authors.forename: Geoff
authors.initials: G
authors.lastname: Denton
mesh_terms: 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
chemical_list: D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D004958:Estradiol; D005640:Follicle Stimulating Hormone