Bioavailability of estradiol from two matrix transdermal delivery systems:: Menorest® and Climara®

Objectives: To compare two estradiol transdermal matrix systems with regard to bioavailability, pharmacokinetics and tolerability. Methods: A single centre, open, randomized, comparative cross-over study in 20 healthy postmenopausal women. Menorest(R) with 3 or 4 days of suggested use and Climara(R) with 7 days of suggested use (both 50 mu g/24 h) were compared at steady state. Two 14-day treatment periods were separated by a 4 week washout. Plasma levels of estradiol were monitored during the second week of each treatment. Tolerability was assessed by open questions and inspection of the application site. Results: There were no differences between the two treatments With regards to AUC, C-max, C-min, C-average or fluctuations of plasma estradiol. T-max was significantly shorter for Menorest(R) than Climara(R). C-max and C-min were significantly higher for the second Menorest(R) patch during the monitoring period compared to the first. Ah local reactions were mild and there were three cases of erythema with Menorest(R) and a total of 21 skin reactions in 15 subjects with Climara. Systemic tolerability was similar between treatments with eight estrogen-related adverse events in eight subjects (period pains, uterine bleeding, mastodynia, headache and vaginal discharge) with Menorest(R) and 13 events in ten subjects with Climara(R). Conclusions: The bioavailability of estradiol from the two matrix transdermal delivery systems Menorest(R) and Climara(R) was similar, but the products were not bioequivalent because T-max was significantly shorter for Menorest(R) than for Climara(R) Tolerability of treatment was good for both patches but with a higher number of local reactions and estrogen related adverse events for Climara(R). (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.