Lg. Gisclon et al., Lack of effect of a high-fat meal on the bioavailability of 17 beta-estradiol/norgestimate in healthy postmenopausal women, J CLIN PHAR, 40(7), 2000, pp. 762-769
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.