17Beta-estradiol delivered by three different matrix patches 50 microg/day: a three way cross-over study in 21 postmenopausal women
- PMID: 10585173
- DOI: 10.1016/s0378-5122(99)00039-0
17Beta-estradiol delivered by three different matrix patches 50 microg/day: a three way cross-over study in 21 postmenopausal women
Abstract
The aim of this study was to investigate the systemic bioavailability and plasma profiles of 17beta-estradiol (E2) after the application of three matrix patches for the transdermal delivery of E2: Menorest, Tradelia, and Estraderm MX claiming to deliver a dosage of 50 microg E2/day. All three patches were each worn randomly by 21 postmenopausal women volunteers over a 4-day period (i.e. 96 h). Each of the three treatment periods were separated by an at least 7 day wash out period according to a randomized, 3-way crossover design. Blood samples were taken from the antecubital vein before and 3, 6, 9, 12, 24, 28, 33, 48, 57, 72, 81, and 96 h after application. E2 plasma values were determined by a specific direct radioimmunoassay method. The following pharmacokinetic parameters were evaluated: AUC0-96h, Cmax, Tmax, Cmin, C(average). The time to reach the maximal E2 value of 32 h was the only pharmacokinetic parameter which was identical for all three patches. Menorest produced the highest E2 bioavailability judged by the AUC0-96h = 3967.8 +/- 1651.8 pg/ml, C(average) = 41.3 +/- 21.3 pg/ml, Cmin = 36.8 +/- 8.6 pg/ml. Tradelia showed statistically not significantly smaller C(average) = 38.9 +/- 17.0 pg/ml, AUC0-96h = 3737.9 +/- 1637.6 pg/ml x per h, and Cmin = 33.8 +/- 26.7 than Menorest. Estraderm MX showed lowest E2 plasma profiles Cmax = 38.9 +/- 25.1 pg/ml, C(average) = 33.2 +/- 17.1 pg/ml, AUC0-96 = 3192.1 +/- 1646.0 pg/ml per x h. Menorest showed the smallest fluctuation over the entire test period, similar to Estraderm MX, while Tradelia showed the highest E2-fluctuation (P < 0.01): Tradelia exhibited the highest Cmax = 48.0 +/- 20.3 pg/ml. When E2 baseline levels, prior to patch application are subtracted individually from the produced E2 plasma level, Estraderm MX is not bioequivalent to Menorest (P < 0.05). A circadian curve pattern of the E2 plasma level was observed for all patches: in the evening higher E2 plasma level were always detected compared with the morning, however, less pronounced with Estraderm MX. Individual comparison of AUC0-96h of each patch exhibited a large interindividual variability of 2000-8000 pg/ml per h for all three patches but relatively small individual variability: women with high E2 bioavailability (high responders) maintained high bioavailability in all applied patches, women identified as low and medium responders remained the same regardless of the applied patch. Menorest produced in 2/3 of all postmenopausal women with the highest E2 bioavailability (AUC0-96h), Tradelia was found in less than 1/3 (28.6%), and Estraderm MX in only one postmenopausal woman. Menorest only produced the highest reduction in postmenopausal symptoms together with Tradelia. Estraderm MX produced a smaller reduction in postmenopausal symptoms compared to Menorest and Tradelia. The observed side-effects were approximately equal in all three patches, with a maximum value after 72 h. It can be concluded that the three patches for the transdermal delivery of E2 claiming to deliver 50 microg E2/day differed from each other in their pharmacokinetic performance, although statistically not significant: Menorest exhibited the highest C(average), AUC and Cmin, and the lowest fluctuation, followed by Tradelia and Estraderm MX.
Similar articles
-
Estradiol.2024 May 15. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. 2024 May 15. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. PMID: 30000355 Free Books & Documents. Review.
-
Comparative bioequivalence studies with Estradot and Menorest transdermal systems.Maturitas. 2003 Nov 20;46(3):187-98. doi: 10.1016/s0378-5122(03)00190-7. Maturitas. 2003. PMID: 14585521 Clinical Trial.
-
Bioavailability of estradiol from two matrix transdermal delivery systems: Menorest and Climara.Maturitas. 2000 Jan 15;34(1):57-64. doi: 10.1016/s0378-5122(99)00088-2. Maturitas. 2000. PMID: 10687883 Clinical Trial.
-
Plasma profiles of transdermal 17 beta-estradiol delivered by two different matrix patches. A four-way cross-over study in postmenopausal women.Arzneimittelforschung. 1997 Jun;47(6):761-7. Arzneimittelforschung. 1997. PMID: 9239456 Clinical Trial.
-
Menorest: technical development and pharmacokinetic profile.Eur J Obstet Gynecol Reprod Biol. 1996 Apr;64 Suppl:S29-33. doi: 10.1016/0301-2115(95)02354-2. Eur J Obstet Gynecol Reprod Biol. 1996. PMID: 8732471 Review.
Cited by
-
Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures.Endocr Connect. 2019 Apr;8(4):360-366. doi: 10.1530/EC-19-0025. Endocr Connect. 2019. PMID: 30851161 Free PMC article.
-
Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes.Cochrane Database Syst Rev. 2004 Oct 18;2004(4):CD002978. doi: 10.1002/14651858.CD002978.pub2. Cochrane Database Syst Rev. 2004. PMID: 15495039 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources