Lack of effect of a high-fat meal on the bioavailability of 17 beta-estradiol/norgestimate in healthy postmenopausal women.
The effect of a high-fat meal on the absorption and pharmacokinetics of 17 beta-estradiol (E2), estrone (E1), estrone sulfate (E1S), and 17-deacetylnorgestimate (17d-NGM) were determined in this two-way complete crossover study of a single dose of E2/NGM (2 mg/180 micrograms) in 24 postmenopausal women. Equal numbers of subjects were randomly assigned to two treatment sequences indicated by the order of fed and fasting treatments. Serial blood samples were collected before and after dosing and assayed using validated methods. Food had no effect on the pharmacokinetics of E2, the pharmacologically active estrogen species. Food increased the rates of formation of E1 and E1S and slowed the formation of 17d-NGM. However, because E1 and E1S are pharmacologically less active metabolites of E2, and since the pharmacokinetic alterations in 17d-NGM were observed over a short time period, these results are probably of no clinical relevance. The extent of formation of all analytes, as measured by AUC, was not affected by food. In conclusion, administration of a tablet containing 17 beta-estradiol/norgestimate (2 mg/180 micrograms) was safe and well tolerated by healthy postmenopausal women and may be given without regard to the timing of meals in relation to dosing.
Gisclon
L G
LG
Robert Wood Johnson Pharmaceutical Research Institute, Spring House, PA 19477, USA.
Curtin
C R
CR
Larson
K L
KL
Natarajan
J
J
Wong
F A
FA
Morrison
D N
DN
Bourg
D
D
D001682:Biological Availability; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000378:metabolism*; D004958:Estradiol / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008875:Middle Aged; D009644:Norgestrel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D017698:Postmenopause / Q000378:metabolism*; D016387:Women's Health
D003280:Contraceptives, Oral, Synthetic; D004041:Dietary Fats; D009644:Norgestrel; D004958:Estradiol; C017576:norgestimate