Characterization of a 7 day 17 beta-estradiol transdermal delivery system: pharmacokinetics in healthy postmenopausal women.
To assess the delivery characteristics of a new 7 day 17 beta-estradiol transdermal delivery system (TDS), estradiol and estrone pharmacokinetics were evaluated following a single 7 d 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 24 h (urine) or 72 h (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 7 d 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 17 beta-estradiol TDS delivered a nominal estradiol dose of 0.02 mg/24 h during the intended wear period.
Boyd
R A
RA
Pharmacokinetics/Drug Metabolism Department, Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, MI 48106-1047, USA.
Zegarac
E A
EA
Eldon
M A
MA
Sedman
A J
AJ
Forgue
S T
ST
D000279:Administration, Cutaneous; D000368:Aged; D019540:Area Under Curve; D018592:Cross-Over Studies; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004970:Estrone / Q000097:blood / Q000652:urine; D005260:Female; D006207:Half-Life; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011863:Radioimmunoassay
D004970:Estrone; D004958:Estradiol