17β‐Estradiol Matrixpatch Removal and Reapplication in Postmenopausal Women: Theoretical Predictions with an Oscillating Diffusion Coefficient Model

Rohr, Uwe D.; Saeger-Lorenz, K.

doi:10.1002/jps.10138

Cited by 8 publications

(8 citation statements)

References 44 publications

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“…A recent article in Obstetrics and Gynecology, written by several key WHI investigators, addresses the same issues by summarizing the WHI data in a rational way. This is in line with that of most non-WHI opinion leaders, supporting the prescription of E2 hormone therapy to young, healthy, symptomatic menopausal women, ascertaining treatment efficacy on the one hand while relieving the worries concerning its safety in this target population on the other hand [2,3].…”

Section: Introductionsupporting

confidence: 67%

“…We therefore decided to investigate the steady state condition for immediate oral delivery. In contrast to our previous steady state investigation with a matrix patch for Table 1 Key characteristics of participating menopausal women [3,4,12].…”

Section: Introductionmentioning

confidence: 97%

“…Although it is concluded among opinion leaders and menopause societies that it is appropriate to treat women with symptoms at the onset of menopause, because there is no proven therapy for primary prevention, in some women the use of HRT for this role may at least be justified [3]. As there is a newly sparked interest in E2 delivery, several questions still remain concerning E2 steady state delivery, the relationship between pharmacokinetics and dynamics, as well as a comparison between oral and transdermal pharmacokinetics and pharmacodynamics.…”

Section: Introductionmentioning

confidence: 97%

“…For many years, the results of both arms of the Women′s Health Initiative (WHI) were translated into very cautious, even negative recommendations in regard to the use of postmenopausal hormones [2,3]. Only recently, the International Menopause Society, the North American Menopause Society and the Endocrine Society expressed their opinions in formal statements, which were generally more favorable.…”

Section: Introductionmentioning

confidence: 98%

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Comparison of steady state development and reduction of menopausal symptoms after oral or transdermal delivery of 17-β-estradiol in young healthy symptomatic menopausal women

Rohr¹,

Volko²,

Schindler³

2014

Hormone Molecular Biology and Clinical Investigation

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There is a difference in the steady state between oral and transdermal E2 delivery. Steady state condition is achieved in the first application of a matrix patch, whereas with the application of a tablet the steady state is achieved in transdermal delivery within 12-14 days. Our reported calculated missed intake of a E2 tablet shows that E2 plasma levels drop for 4 days consecutively. Our conducted study has several limitations: firstly, no cross-over was conducted, but a rather cumbersome mathematical modeling; secondly, healthy women with no accompanying severe diseases were included in this study. The higher the oral dose, the higher the E2 steady state levels, but the time to achieve steady state levels is independent from the E2 dose.

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Section: Introductionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

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Comparison of steady state development and reduction of menopausal symptoms after oral or transdermal delivery of 17-β-estradiol in young healthy symptomatic menopausal women

Rohr¹,

Volko²,

Schindler³

2014

Hormone Molecular Biology and Clinical Investigation

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“…The plasma concentration was calculated based on the drug dissolved matrix/skin bi-layer/one compartment model. The matrix parameters, thickness, diffusion coefficient, partition coefficient and initial concentration, were referred from Rohr and Seager-Lorenz 24) and the pharmacokinetic parameters in human were referred from Baifour and Heel 25) and Gilman et al 26) The parameters used for the simulation are given in each figure caption. The simulated profile well agreed with the experimental and clinical data.…”

Section: Simulation Of Skin Penetration and Plasma Concentration Profilementioning

confidence: 99%

Prediction of Percutaneous Absorption in Human Using Three-Dimensional Human Cultured Epidermis LabCyte EPI-MODEL

Hikima

Kaneda

Matsuo

et al. 2012

Biological & Pharmaceutical Bulletin

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The objective of this study is to establish a relationship of the skin penetration parameters between the three-dimensional cultured human epidermis LabCyte EPI-MODEL (LabCyte) and hairless mouse (HLM) skin penetration in vitro and to predict the skin penetration and plasma concentration profile in human. The skin penetration experiments through LabCyte and HLM skin were investigated using 19 drugs that have a different molecular weight and lipophilicity. The penetration flux for LabCyte reached 30 times larger at maximum than that for HLM skin. The human data can be estimated from the in silico approach with the diffusion coefficient (D), the partition coefficient (K) and the skin surface concentration (C) of drugs by assuming the bi-layer skin model for both LabCyte and HLM skin. The human skin penetration of β-estradiol, prednisolone, testosterone and ethynylestradiol was well agreed between the simulated profiles and in vitro experimental data. Plasma concentration profiles of β-estradiol in human were also simulated and well agreed with the clinical data. The present alternative method may decrease human or animal skin experiment for in vitro skin penetration.Key words in silico correlation; reconstructed epidermis; LabCyte EPI-MODEL; hairless mouse Human skin permeability of drugs in vivo can be estimated from in vitro experiment using human skin. However, some researchers have ethical and cultural difficulty to get human skins. Thus, animal skins have been widely used for pharmaceutical, toxicological and cosmetic R&D although the skins have a species difference between human. Recently, the 7th Amendment of the EC Cosmetic Directive prohibits the sale of cosmetics and ingredients validated their safety by animal testing with an alternative method. 1) Thus, researchers utilize reconstructed human skin instead of animal skin. The experiments used reconstructed epidermis is approved by the European Centre for the Validation of Alternative Methods (ECVAM) as the scientifically validated methods for skin corrosion and irritation. 2,3) Permeability studies with Episkin ® , EpiDerm TM and SkinEthic ® comparison to human and animal skin were investigated and the authors reported that the penetration flux through the reconstructed skin was higher than that of skin. [4][5][6] The OECD regulations accepted the results from the reconstructed skin 7) but don't approve it as an alternative method for in vitro human skin penetration experiment yet.Skin penetration is widely expressed by the mathematical models on the basis of the process of diffusion and dissolution. Penetration parameters, diffusion coefficient D [cm 2 /s] and partition coefficient K [-], through stratum corneum (SC) and viable skin (VS) of hairless mouse skin are found to well agree with that of human skin. 8) Not only the skin penetration profile but the blood concentration profile in human is well simulated using the penetration parameters determined from hairless mouse skin, the thickness of human SC and VS, the skin enzymatic parameters (first-ord...

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Repeated applications of a transdermal patch: Analytical solution and optimal control of the delivery rate

Simon

2007

Mathematical Biosciences

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17β‐Estradiol Matrixpatch Removal and Reapplication in Postmenopausal Women: Theoretical Predictions with an Oscillating Diffusion Coefficient Model

Cited by 8 publications

References 44 publications

Comparison of steady state development and reduction of menopausal symptoms after oral or transdermal delivery of 17-β-estradiol in young healthy symptomatic menopausal women

Comparison of steady state development and reduction of menopausal symptoms after oral or transdermal delivery of 17-β-estradiol in young healthy symptomatic menopausal women

Prediction of Percutaneous Absorption in Human Using Three-Dimensional Human Cultured Epidermis LabCyte EPI-MODEL

Repeated applications of a transdermal patch: Analytical solution and optimal control of the delivery rate

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