Estradiol and estrone plasma levels during application of three strengths of a 7-day estradiol transdermal patch

Background: A new estradiol transdermal patch was developed for a once week ly application, with the aim to achieve an optimum practicability and to im prove long-term compliance with estrogen replacement therapy. The pharmacok inetics of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) during a 7- day application of the new patch is reported in this publication. Methods. Unconjugated estradiol and estrone were assayed in plasma in a thr ee-way crossover study on 18 postmenopausal women during and after a 7-day application of 3 strengths of the new patch, with daily release rates of 25 , 50 and 75 mu g of estradiol. Results: During the 7-day application of the transdermal patches the concen tration in plasma of unconjugated estradiol Increased from less than 5 pg/m l, typical of postmenopause. to average concentrations of 26, 49 and 66 pg/ ml under the patches with the release rates of 25, 50 and 75 mu g/day of es tradiol, respectively. The increases were linearly related and proportional to the strength of the patches. Upon removal of the patches, the estradiol concentrations returned to the basal postmenopausal values in 8-24 h. Reta rded with regard to estradiol, there was also an increase of unconjugated e strone, from basal concentrations of 24 pg/ml to average concentrations of 39, 54 and 62 pg/ml, respectively. Estrone returned to basal concentrations 24-48 h after removal of the patches. The estradiol/estrone ratio from the low pretreatment values of 0.15-0.21 typical of postmenopause increased to average values of 0.51, 0.92 and respectively 1.09 during the application of the patches with the three strengths. The ratios are in the range of tho se of unconjugated hormones during the fertile age of women. The patches Mere well tolerated by the skin, with rare mild and transient r eactions that disappeared spontaneously and did not cause interruption of t reatment. Also the systemic tolerability was food, with occasional mild or moderate side effects typical of estradiol found especially under the appli cation of the two higher strengths, i.e, with release of 50 and of 75 mu g/ day of estradiol. Conclusions: The effective pharmacokinetic performance over the 7-day appli cation, combined with the good general and local tolerability and the need to apply the patches only once weekly confer to the new patches a favorable practicability for the long-term estrogen replacement therapy needed to co ntrol the most severe postmenopausal disorders.