Lack of effect of a high-fat meal on the bioavailability of 17β-estradiol/norgestimate in healthy postmenopausal women.

The effect of a high-fat meal on the absorption and pharmacokinetics of 17β-estradiol (E 2 ), estrone (E 1 ), estrone sulfate (E 1 S), and 17-deacetylnorgestimate (17d-NGM) were determined in this two-way complete crossover study of a single dose of E 2 /NGM (2 mg/180 μg) 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 E 2 , the pharmacologically active estrogen species. Food increased the rates of formation of E 1 and E 1 S and slowed the formation of 17d-NGM. However, because E 1 and E 1 S are pharmacologically less active metabolites of E 2 , 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 byAUC, was not affected by food. In conclusion, administration of a tablet containing 17β-estradiol/norgestimate (2 mg/180 μg) was safe and well tolerated by healthy postmenopausal women and may be given without regard to the timing ofmeals in relation to dosing.