Comparative bioequivalence studies with Estradot and Menorest transdermal systems

To compare the relative bioavailability of Estradot, a small size, new generation estradiol transdermal system (ETS) to Menorest, in healthy postmenopausal women.

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 microg/day), 10 cm(2) (100 microg/day) Estradot and 29 cm(2) (100 microg/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 microg/day) new generation patch, Estradot and a 14.5 cm(2) (50 microg/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.

In Study 1, baseline-uncorrected C(max) for estradiol for Estradot 50 and 100 microg/day and Menorest 100 microg/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 microg/day and Menorest 50 microg/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.

Estradot produced comparable serum concentrations of estradiol and estrone and caused less skin irritation than Menorest.