Abstract
Circulating levels of 17β estradiol (E2) following the administration of fixed doses of E2, show a great variability in kinetics depending upon the product administrated, the routes of administration, and the interindividual variations in absorption and metabolism. This might have important implications both in terms of tolerance and effectiveness. Two new forms of transdermal E2 (SYSTEN® Cilag and MENOREST® Rhone-Poulenc Rorer) have been recently accepted in Europe for the treatment of climacteric symptoms. The present study was undertaken to compare the pharmacokinetic characteristics of plasma E2 profile under these two drugs. It was carried out in 30 healthy postmenopausal volunteers according to good clinical practice after informed consent, as a single blind, randomised, cross-over study during the classical wearing period of 4 days. Plasma E2 concentration was determined 24 hours before, 1/2 hour before and then 2, 4, 8, 12, 24, 48, 72, 84, 96 hours after the first patch administration. E2 measurement was performed using a specific direct radioimmunoassay developed in the FRH laboratories. The main criteria for this method were an intraassay coefficient of variation (CV) less than 6%, an interassay CV less than 8% in a concentration range of 15-140 pg/ml and a quantitative detection limit (LOQ) of 2.7 pg/ml with a 20% CV. The following kinetic parameters were analysed: Cmax, Cmean, C96 and MRT. The bioequivalence was assessed by analysis of variance of Cmax, Cmean, C96 and AuC after logarithmic transformation, complemented by Westlake test (95%). Data show that these two products are identical in terms of Cmax but Cmean, C96 and AuC are statistically greater when MENOREST 50(R) is administered; furthermore, E2 levels decrease more rapidly and more deeply with SYSTEN 50®than MENOREST 50®
The differences of pharmacokinetic profiles after administration of two different forms of the same dose of 50 μg transdermal 17 β estradiol might have important medical consequences.