PHARMACOKINETICS OF A 7-DAY 17-BETA-ESTRADIOL TRANSDERMAL DELIVERY SYSTEM - EFFECT OF APPLICATION SITE AND REPEATED APPLICATIONS ON SERUM CONCENTRATIONS OF ESTRADIOL AND ESTRONE

FemPatch (Parke-Davis Pharmaceutical Research, Division of Warner-Lamb ert Company, Ann Arbor, MI), a new 7-day 17 beta-estradiol transdermal delivery system (TDS), has been developed for treatment of menopausal vasomotor symptoms. This two-period crossover study was conducted to determine the effects of TDS application site (buttocks versus abdomen ) and early TDS replacement on estradiol and estrone concentrations, a nd to quantify intersubject and intrasubject pharmacokinetic variabili ty. Eighteen healthy, postmenopausal female volunteers received a sing le 7-day TDS application to the abdomen and repeated TDS applications to the buttocks (regular replacement on days 7 and 14, intentional ear ly replacement on day 17, and removal on day 21). Serial serum samples were assayed for estradiol and estrone by validated radioimmunoassay methods. The 7-day TDS delivers estradiol at a constant, near zero-ord er rate for the duration of application, independent of application si te. Mean serum estradiol concentrations were higher after application to the buttocks than after application to the abdomen (19 and 15 pg/mL above baseline, respectively), making the buttocks the preferred site for TDS application. Mean serum concentration of estradiol was slight ly higher (23 pg/mL above baseline) for the treatment week with early TDS replacement due to the transient increase in concentration over th e first 24 hours after replacement. Parallel but smaller increases in concentrations of estrone were observed. Serum estradiol and estrone c oncentrations are reproducible within an individual from application t o application (coefficient of variation, 25%). Variability between ind ividuals was higher (coefficient of variation, 40-50%).