Pharmacokinetics and bioavailabilty of an ultra low dose estradiol transdermal system in healthy postmenopausal women

Background Decreased levels of estrogens seen in postmenopausal women may result in the development of osteoporosis and fractures. Elderly women with endogenous E2 concentration between 10 and 25 pg/mL show greater bone mineral density over women who have undetectable E2 concentration. The present study was designed to evaluate the pharmacokinetics (PK) of 17β-estradiol (E2) and to determine its daily delivery rate from an ultra low dose E2 3.25 cm2 transdermal delivery system (ULD TDS) in comparison with a marketed Climara® 6.5 cm2 TDS (CTDS, 25 μg E2/day). Methods Eighteen postmenopausal women (60 to 80 years old) were enrolled in an IRB approved, open-label, randomized, 2-period, 2-treatment, cross-over study. Each woman received a single transdermal application of an ULD TDS and CTDS with a 3-week washout between study periods. Serum samples were analyzed for E2 using a validated GC/MS method. PK analysis was performed using standard non-compartmental Analysis. Results Both transdermal systems were well tolerated and had excellent adhesion properties. No serious adverse events were reported. The mean E2 serum concentration profile for the ULD TDS was consistent with a steady E2 delivery throughout the seven-day wear period with an average serum concentration of 13.7 pg/mL, The rate and extent of absorption of E2 from the ULD TDS was approximately half of that of CTDS. The average in vivo daily delivery rate of the ULD TDS was 14 μg (95% CI 12 - 16 μg). Conclusions In postmenopausal women, ULD TDS maintains average serum E2 concentration with a range that has been associated with increased bone mineral density and thus is preventive of osteoporosis. Clinical Pharmacology & Therapeutics (2004) 75, P58–P58; doi: 10.1016/j.clpt.2003.11.220