Transdermal delivery of estradiol in postmenopausal women with a novel topical aerosol.
The objective of this study was to determine if a novel metered-dose topical aerosol (MDTA) formulation containing the new dermal penetration enhancer, padimate O, could enhance the transdermal delivery of estradiol to an extent that would result in clinically relevant plasma concentrations. The estradiol MDTA (with padimate O) was applied once daily at 0800 h to postmenopausal women for 9 days, and plasma estradiol and estrone was measured daily (24 h postapplication) by radioimmunoassay. The topical dose was administered as three 1 mg doses of estradiol, each applied as a single spray over 10 cm2 which were placed adjacent to each other on the subject's ventral forearm. None of the subjects tested showed any sign of skin irritation at the application site over the entire study period using the Draize irritation score. In four postmenopausal women (age 54-63 years, weight 67-93 kg) the mean estradiol level 24 h postapplication over the 9 day study period was 53 pg/mL. This result was significantly greater (p < 0.001) than the baseline value of 13 pg/mL. The mean estradiol/estrone ratio also rose significantly (p < 0.04) from a baseline value of 0.2 up to 0.8. We conclude that this novel MDTA formulation significantly enhances the transdermal delivery of estradiol to allow a clinically relevant dose of estradiol to be delivered in postmenopausal women with once daily dosing.
Morgan
T M
TM
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
O'Sullivan
H M
HM
Reed
B L
BL
Finnin
B C
BC
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000336:Aerosols; D000368:Aged; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011863:Radioimmunoassay; D012869:Skin Absorption / Q000187:drug effects; D062366:para-Aminobenzoates
D000336:Aerosols; D062366:para-Aminobenzoates; D004970:Estrone; D004958:Estradiol; D010129:4-Aminobenzoic Acid; C041981:padimate-O