[en] OBJECTIVE: A new matrix 17 beta-estradiol transdermal patch incorporating lauric acid to improve estradiol skin absorption has been designed for hormone replacement therapy. Estradiol pharmacokinetics obtained with the prototype, its industrial counterpart, a matrix-type, System 50, and a reservoir-type, Estraderm TTS 50, transdermal patch have been compared. Each device delivers 50 micrograms estradiol daily. METHODS: Twenty postmenopausal women received each of the four formulations for 3 days in a Latin-square design and with a minimum 4-day wash-out period between treatments. Estradiol plasma concentrations were measured by radioimmunoassay at 6, 12, 24, 48 and 72 h after application. RESULTS: The prototype patch and its industrial counterpart showed no significant difference in estradiol delivery, with 72-h systemic exposure to estradiol similar to that of the reservoir patch but greater than that of the reference matrix formulation, with average baseline-corrected concentrations (SEM) of 35 (4), 32 (3), 32 (2) and 19 (1.8) pg/ml, respectively. In addition, they ensured more stable delivery, with coefficients of variation of plasma estradiol concentrations (12-72 h) of 29, 41, 63 and 84%, respectively. All matrix patches demonstrated the same patients to be poor estradiol absorbers, different from those encountered with the reservoir patch type, despite an improved estradiol bioavailability with the lauric acid-containing matrix patch. CONCLUSION: Matrix patches incorporating lauric acid led to estradiol plasma levels more stable than with the reference matrix and reservoir patches, and greater than those with the reference matrix patch.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Donazzolo, Y.
Brion, N.
Lins, R.
Language :
English
Title :
Estradiol Pharmacokinetics after Transdermal Application of Patches to Postmenopausal Women: Matrix Versus Reservoir Patches
Publication date :
September 2000
Journal title :
Climacteric: the Journal of the International Menopause Society
Lievertz R.W. (1987) Pharmacology and pharmacokinetics of estrogens. Am J Obstet Gynecol 156:1289-1293.
Judd H.L. (1987) Oestrogen replacement therapy: Physiological considerations and new applications. Bailliere's Clin Endocrinol Metab 1:177-206.
Kuhnz W., Gansau C., Mahler M. (1993) Pharmacokinetics of estradiol, free and total estrone, in young women following single intravenous and oral administration of 17β-estradiol. Arzneim Forsch 43:966-973.
Steingold K.A., Laufer L., Chetkowski R.J. (1985) Treatment of hot flashes with transdermal estradiol treatment. J Clin Endocrinol Metab 61:627-632.
Selby P.L., McGarricle H.H.G., Peacock M. (1989) Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women. Clin Endocrinol 30:241-249.
Marty J.P. (1996) New trends in transdermal technologies: Development of the skin patch, Menorest(®). Int J Gynecol Obstet 52:17-20.
Balfour J., Heel R. (1990) Transdermal estradiol. A review of its pharmacodynamic properties, and therapeutic efficacy in the treatment of postmenopausal complaints. Drugs 40:561-582.
Reginster J.Y., Albert A., Deroisy R. (1997) Plasma estradiol concentrations and pharmacokinetics following transdermal application of Menorest® 50 or Systen® (Evorel®) 50. Maturitas 27:179-186.
Berner B., John V.A. (1994) Pharmacokinetic characterisation of transdermal delivery systems. Clin Pharmacokinet 26:121-134.
Johnson W. (1999) Amended final report on the safety assessment of hydroxystearic acid. Int J Toxicol 18:1-10.
Walters K.A. (1989) Penetration enhancers and their use in transdermal therapeutic systems., Hadgraft J, Guy RH, eds. Drugs Pharmaceutical Sciences - Transdermal Drug Delivery. New York: Marcel Dekker; 35:197-246.
Rohr U.D., Nauert C., Stehle B. (1999) 17β-Estradiol delivered by three different matrix patches 50 μg/day. A three way cross-over study in 21 postmenopausal women. Maturitas 33:45-58.
O'Connell M.B. (1995) Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol 35.
Muller P., Botta L., Ezzet F. (1996) Bioavailability of estradiol from a new matrix and a conventional reservoir-type transdermal therapeutic system. Eur J Clin Pharmacol 51:327-330.
Le Roux Y., Borg M.L., Thebault J. (1995) Bioavailability study of Menorest®, a new estrogen transdermal delivery system, compared with a transdermal reservoir system. Clin Drug Invest 10:172-178.
Setnikar I., Rovati L.C., Vens-Cappell B. (1996) Bioavailability of estradiol from two transdermal patches. Arzneim Forsch 46:307-310.
(1993) A randomized study to compare the effectiveness, tolerability and acceptability of two different transdermal replacement therapies. Int J Fertil 38:5-11.