Dose proportionality study of four doses of an estradiol transdermal system, Estradot®

Abstract

Objectives: To establish dose proportionality among four doses of a new estradiol transdermal system (ETS), Estradot®, in healthy postmenopausal women and to evaluate the wear and irritation properties of the ETS. Methods: In an open label, single-dose, randomized, four-period crossover study, healthy postmenopausal women, age range 44–64 years, wore four different sizes of Estradot, 2.5, 3.75, 5.0 and 10.0 cm 2 that were expected to release estradiol at 0.025, 0.0375, 0.05 and 0.10 mg/day, respectively. Each patch was worn for 84 h with a 7-day washout period between treatments. Blood samples were drawn prior to medication, then at various time points following patch application. Serum concentrations of estradiol and estrone were determined by validated gas chromatography/mass spectrometry (GS/MS) methods. Skin irritation, (erythema and edema), patch adherence and local skin reaction were assessed and recorded following patch removal. After removal, the patches were assayed for residual estradiol to estimate the apparent dose delivered. Results: The baseline-corrected, mean maximum serum estradiol concentrations (C max) for the 2.5, 3.75, 5.0 and 10.0 cm 2 patches were 24.0, 34.8, 50.1 and 96.0 pg/ml, respectively, and for estrone were 10.5, 15.2, 21.8 and 41.0 pg/ml, respectively. The four Estradot patches adhered well during the study. No significant skin irritation was observed with any of the four treatments. Conclusions: The results indicate a dose proportional relationship of increased serum concentrations of estradiol with increasing size of the Estradot patches. The four doses of Estradot demonstrated good systemic and local skin tolerability.