A randomized, multiple-dose parallel study to compare the pharmacokinetic parameters of synthetic conjugated estrogens, A, administered as oral tablet or vaginal cream.
OBJECTIVE
A randomized, parallel-design study was conducted to determine the pharmacokinetic profile of synthetic conjugated estrogens A (SCE-A) vaginal cream (0.625 mg SCE-A/g) when administered at intervals (1 g once daily for 7 d, then twice weekly) over a 27-day period as compared with the pharmacokinetic profile of 0.3 mg SCE-A tablets administered once daily orally for 27 days.


METHODS
Blood samples were collected 48 hours before initial dosing for baseline levels and at multiple occasions during the study until 48 hours after final study dosing (day 29). Maximum plasma concentration, time to maximum plasma concentration (Tmax), and area under the curve from 0 to 24 hours were calculated at days 1, 7, and 27; in addition, area under the curve from 0 to 48 hours was calculated at days 7 and 27, and area under the curve weekly (AUCweekly) values were calculated for both groups. For purposes of comparison, ratios of AUCweekly values for vaginal cream and oral tablets were analyzed.


RESULTS
Compared with an oral daily dose of 0.3 mg SCE-A, the steady-state systemic exposure from vaginal cream application was considerably less, with the cream-to-oral ratio being 0.45 for baseline-adjusted (BA) unconjugated estradiol, 0.30 for BA unconjugated estrone, and 0.04 for unconjugated equilin (AUCweekly). At steady-state, the systemic blood levels of BA unconjugated estrone, BA unconjugated estradiol and unconjugated equilin were significantly lower in women who received biweekly application of 1 gm vaginal cream compared to women who took an oral daily dose of 0.3 mg SCE-A tablet.


CONCLUSIONS
After intravaginal application of SCE-A vaginal cream, absorption of estrogens was lower compared with absorption after oral administration. At steady state, the systemic exposure of equilin, estradiol, and estrone was significantly lower after twice-weekly administration of 1 g SCE-A vaginal cream compared with that achieved with an oral daily dose of a 0.3 mg SCE-A tablet.
Teva Branded Pharmaceuticals USA, Woodcliff Lake, NJ, USA.
Rupinder K
RK
Bhamra
Marya B
MB
Margolis
James H
JH
Liu
Christopher H
CH
Hendy
Rand G
RG
Jenkins
Charles E
CE
DiLiberti
D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D004857:Equilin / Q000097:blood; D004958:Estradiol / Q000097:blood; D045166:Estradiol Congeners / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004967:Estrogens / Q000008:administration & dosage / Q000493:pharmacokinetics; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D017698:Postmenopause; D013607:Tablets / Q000008:administration & dosage*; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage*
D045166:Estradiol Congeners; D004967:Estrogens; D013607:Tablets; D014622:Vaginal Creams, Foams, and Jellies; D004857:Equilin; D004970:Estrone; D004958:Estradiol; C509653:estrogens, conjugated synthetic A