Pharmacokinetics of continuous once-a-week combination 17β-Estradiol/Low- or high-dose levonorgestrel transdermal delivery systems in postmenopausal women.
Two open-label, randomized, two-period, crossover studies were performed to determine the safety, delivery rates, and pharmacokinetic properties of a combination estradiol (E2)/levonorgestrel (LNG) transdermal delivery system (TDS). Study 1 enrolled 24 postmenopausal women who received a single TDS containing 4.4 mg E2 and 1.39 mg of LNG (E2/LNG Low) or E2 0.050 mg/24 hours TDS and 0.090 mg LNG oral tablet. Study 2 enrolled 44 postmenopausal women who received either E2/LNG Low or TDS containing 4.4 mg E2 and 2.75 mg LNG (E2/LNG High) weekly for a period of 4 weeks. E2, estrone (E1), LNG, and sex hormone-binding globulin (SHBG) serum concentrations were determined. Overall, both E2/LNG TDS were well tolerated and had excellent adhesion properties. The average daily delivery for E2/LNG Low was 0.045 mg for E2 and 0.0132 mg for LNG. Following weekly delivery of E2/LNG Low or High for 4 weeks, the combination of E2 with two different strengths of LNG did not alter the pharmacokinetic profile of E2. SHBG, total cholesterol, and triglycerides concentrations significantly decreased compared to baseline. Both E2/LNG Low and High TDSs were well tolerated and provided continuous drug delivery over 7 days supporting the benefits of the transdermal route of administration in optimally delivering hormonal therapy.
School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD, USA.
Adel H
AH
Karara
3M Drug Delivery Systems, Saint Paul, MN, USA.
Lester I
LI
Harrison
Drug Development Resources, LLC, Williamsburg, VA, USA.
Armen P
AP
Melikian
Sunovion Pharmaceuticals, Inc., Fort Lee, NJ, USA.
Nagaraju
N
Poola
QPS Bio-kinetic, Springfield, MO, USA.
Dennis
D
Morrison
QPS Bio-kinetic, Springfield, MO, USA.
Dale
D
Bourg
QPS Bio-kinetic, Springfield, MO, USA.
Linda
L
Bourg
Bayer Pharma AG, GDD-Clinical Pharmacokinetics, Berlin, Germany.
Christian
C
Zurth
D000279:Administration, Cutaneous; D000368:Aged; D018592:Cross-Over Studies; D004338:Drug Combinations; D016503:Drug Delivery Systems; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004970:Estrone / Q000097:blood; D004997:Ethinyl Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
D004338:Drug Combinations; D004967:Estrogens; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D004997:Ethinyl Estradiol; D004958:Estradiol; D016912:Levonorgestrel
combination hormone therapy; estradiol; levonorgestrel; postmenopausal women; transdermal delivery systems