Characterization of a 7 day 17β-estradiol transdermal delivery system : Pharmacokinecits in healthy postmenopausal women

To assess the delivery characteristics of a new 7 day 17β-estradiol transdermal delivery system (TDS), estradiol and estrone pharmacokinetics were evaluated following a single 7d application of one TDS or two TDSs in 24 healthy, postmenopausal women in a nonblind, randomized, two-period crossover study. Serial blood samples and total urine output were collected before (baseline measurement of endogenous hormone) and during TDS application, and for 24h (urine) or 72h (blood) following TDS removal. Serum was assayed for estradiol and estrone by a validated radioimmunoassay (RIA) method. The combined amounts of estradiol and its conjugates, and estrone and its conjugates in urine were determined by validated RIA methods. Overall, one or two estradiol TDSs were well tolerated by healthy, postmenopausal female volunteers. Estradiol absorption from the TDS was characterized by a zero-order process and was dose proportional, resulting in average steady-state serum estradiol concentrations of 16 and 33 pg mL -1 above baseline during the 7d application of one and two TDSs, respectively. Parallel but smaller increases in serum estrone concentrations were observed, resulting in an increase in the serum estradiol/estrone concentration ratio from approximately 0.2 at baseline to median values of 0.64 and 0.88 during application of one and two TDSs, respectively. The 7 day 17β-estradiol TDS delivered a nominal estradiol dose of 0.02 mg/24 h during the intended wear period.