Comparative bioequivalence studies with Estradot® and Menorest® transdermal systems

Abstract

Objectives: To compare the relative bioavailability of Estradot®, a small size, new generation estradiol transdermal system (ETS) to Menorest®, in healthy postmenopausal women. Methods: In two open-label, single center, randomized, crossover, bioequivalence studies, healthy postmenopausal women aged 40–65 years received treatment with all the test regimens. In Study 1 (single-dose study), patients wore 5 cm 2 (50 μg/day), 10 cm 2 (100 μg/day) Estradot and 29 cm 2 (100 μg/day) Menorest for 84 h. In Study 2 (multiple-dose study), patients wore a regimen of four consecutive treatments with a 5 cm 2 (50 μg/day) new generation patch, Estradot and a 14.5 cm 2 (50 μg/day) patch, Menorest. Blood samples were drawn at various time-points in both studies. Estradiol and estrone serum levels were determined by gas chromatography/mass spectrometry or radioimmunoassay methods. Skin irritation (erythema and edema), patch adherence and local skin reaction were assessed following patch removal. Results: In Study 1, baseline-uncorrected C max for estradiol for Estradot 50 and 100 μg/day and Menorest 100 μg/day was 54.8, 106.2 and 101.6 pg/ml, respectively, and C max for estrone was 75.6, 97.0 and 98.3 pg/ml, respectively. In Study 2, the baseline-uncorrected mean maximum serum concentration (C max) for estradiol for Estradot 50 μg/day and Menorest 50 μg/day patches was 56.7 and 52.7 pg/ml, respectively, and C max for estrone was 41.7 and 41.3 pg/ml, respectively. No significant skin irritation was observed in either study, but Estradot caused less skin irritation than Menorest. Conclusions: Estradot produced comparable serum concentrations of estradiol and estrone and caused less skin irritation than Menorest.