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 (E-2), estrone (E-1), estrone sulfate (E1S), and 17-deacetyl norgestimate (17d-NGM) were determined in this two-way complete crossover s tudy of a single dose of E-2/NGM (2 mg/180 mu g) in 24 postmenopausal women . Equal numbers of subjects were randomly assigned to two treatment sequenc es indicated by the order of fed and fasting treatments. Serial blood sampl es were collected before and after dosing and assayed using validated metho ds. Food had no effect on the pharmacokinetics off,, the pharmacologically active estrogen species. Food increased the rates of formation of E-1 and E 1S and slowed the formation of 17d-NGM. However because E-1 and E1S are pha rmacologically less active metabolites of E-2,, and since the pharmacokinet ic alterations in 17d-NGM were observed over a short time period, these res ults are probably of no clinical relevance. The extent of formation of all analytes, as measured by A UC, was not affected by food, In conclusion, adm inistration of a tablet containing 17 beta-estradiol/norgestimate (2 mg/180 mu g) was safe and well tolerated by healthy postmenopausal women and may be given without regard to the timing of meals in relation to dosing.