The effects of skin-to-skin contact, application site washing, and sunscreen use on the pharmacokinetics of estradiol from a metered-dose transdermal spray.

ABSTRACT

OBJECTIVE: This study evaluated the transfer of estradiol by skin-to-skin contact and the influence of washing and sunscreen use on the absorption of estradiol from a transdermal spray. DESIGN: Studies were conducted in the same group of 20 healthy postmenopausal women over a period of 18 days. The women were dosed with three sprays of study medication once daily (a total daily dose of 4.59 mg). To evaluate skin-to-skin transfer, estradiol levels in 20 untreated men were evaluated before and after direct skin-to-skin contact with the application sites of 20 treated women after application of study medication on study days 1 to 3. To examine the effect of washing the application site, estradiol absorption was evaluated when the application site was washed 1 hour after application compared with the unwashed site on study days 10 to 12. To examine the effects of sunscreen use, estradiol pharmacokinetic profiles were evaluated when sunscreen was applied before and after study drug application on study days 14 to 17. RESULTS: The 90% CI of the ratios of the areas under the serum estradiol-time curves (AUC0-24) in untreated men before and after contact with treated women was 1.00 to 1.07, which was within the prespecified equivalence range (0.8-1.25). The 90% CI of the AUC0-24 ratios with and without application site washing was 0.92 to 1.15. Application of sunscreen 1 hour after study drug resulted in a 90% CI of AUC0-24 ratios of 0.76 to 1.08. Application of sunscreen 1 hour before study drug resulted in a 90% CI of AUC0-24 ratios of 0.86 to 1.23. CONCLUSIONS: The use of a transdermal estradiol spray did not result in a significant transfer of estradiol by skin-to-skin contact. Washing the application site did not significantly affect absorption of estradiol. Estradiol absorption was slightly decreased due to the application of sunscreen after study drug application, but was unaffected when sunscreen was applied before study drug.