Skin Penetration and Metabolism of Topical Glucocorticoids in Reconstructed Epidermis and in Excised Human Skin

  title={Skin Penetration and Metabolism of Topical Glucocorticoids in Reconstructed Epidermis and in Excised Human Skin},
  author={Anja Gysler and Burkhard Kleuser and Wolfgang Sippl and Katharina Lange and Hans Christian Korting and Hans-Dieter H{\"o}ltje and Monika Sch{\"a}fer-Korting},
  journal={Pharmaceutical Research},
AbstractPurpose. To investigate pharmacokinetic differences between the non-halogenated double ester prednicarbate (PC) and the fluorinated monoester betamethasone 17-valerate (BM17V) their metabolism in human keratinocytes and fibroblasts as well as their permeation and biotransformation in reconstructed epidermis and excised human skin was compared. Special attention was given to the 17-monoesters because of their high receptor affinity and antiproliferative effects. Methods. Glucocorticoid… 
Esterase activity in excised and reconstructed human skin--biotransformation of prednicarbate and the model dye fluorescein diacetate.
  • F. M. Bätz, W. Klipper, M. Schäfer-Korting
  • Biology, Medicine
    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
  • 2013
Albumin effects on drug absorption and metabolism in reconstructed epidermis and excised pig skin.
Surprisingly, the addition of BSA to the acceptor medium slightly reduced the steroid permeation, especially when formulations of poor PC uptake were tested, and the metabolite pattern changed as compared to PC metabolites to be found in albumin-free acceptormedium.
The impact of skin viability on drug metabolism and permeation -- BSA toxicity on primary keratinocytes.
In vitro skin absorption and drug release - a comparison of six commercial prednicarbate preparations for topical use.
Testosterone Metabolism in Human Skin Cells in vitro and Its Interaction with Estradiol and Dutasteride
Dutasteride may be useful in acne and androgenetic alopecia and regulates testosterone action by cell-type-specific activation or deactivation, and effects of 17α-estradiol in androgenetics alopECia are not due to 5α-reductase inhibition.
Drug Targeting by Solid Lipid Nanoparticles for Dermal Use
Interestingly, PC incorporation into nanoparticles appeared to induce a localizing effect in the epidermal layer which was pronounced at 6 h and declined later, and may increase the benefit/risk ratio of topical therapy.
The Phenion® Full-Thickness Skin Model for Percutaneous Absorption Testing
The Phenion FT model appears to be suitable for percutaneous absorption studies in hazard analysis and should be subjected to a catch-up validation study.
Cyproterone Acetate Loading to Lipid Nanoparticles for Topical Acne Treatment: Particle Characterisation and Skin Uptake
Topical CPA treatment of skin diseases should reduce side effects currently excluding the use in males and demanding contraceptive measures in females and may be an additional therapeutic option for acne and other diseases of the pilosebaceous unit.
Reconstructed Human Epidermis for Skin Absorption Testing: Results of the German Prevalidation Study
A protocol based on the OECD principles was developed and prevalidated by using reconstructed human epidermis (RHE) to standardise the predictive testing of percutaneous absorption for regulatory purposes, and the permeation of the OECD standard compounds, caffeine and testosterone, through commercially available RHE models was compared to that of human epidersmis and animal skin.


Prednicarbate Biotransformation in Human Foreskin Keratinocytes and Fibroblasts
Based on the results to the in-vivo situation, topically applied PC may be metabolized by epidermal cells during skin penetration, a complex mixture of compounds reaches the dermis, whose fibroblasts are barely able to metabolize the steroids.
Prednicarbate Versus Conventional Topical Glucocorticoids: Pharmacodynamic Characterization In Vitro
Correlating antiphlogistic effects in keratinocytes with antiproliferative effects in fibroblasts suggests the improved benefit−risk ratio of PC compared to conventional glucocorticoids does not result only from distinct drug metabolism in the skin but also from a specific influence on the cytokine network.
The effect of the vehicle formulation on the stratum corneum penetration characteristics of clobetasol 17‐propionate in vivo
The multiple skin surface biopsy technique to measure stratum corneum (SC) penetration characteristics in vivo has been more accurately quantified and used to provide information on the kinetics of
In vivo correlation between stratum corneum reservoir function and percutaneous absorption.
The quantity of substance penetrating through intact rat skin can be predicted by measuring the horny layer concentration, and in terms of penetration there is a factor of 50 between benzoic acid (best) and dexamethasone (worst).
application of the human dermal model skin(2) ZK 1350 to phototoxicity and skin corrosivity testing.
Comparison of the effects of calcipotriol, prednicarbate and clobetasol 17-propionate on normal skin assessed by ultrasound measurement of skin thickness.
In contrast to the glucocorticosteroid-induced atrophy, calcipotriol application on normal skin leads to an increase in skin thickness in all volunteers, and the cause seems to be an irritative reaction of the skin which was histologically investigated in one volunteer.
Glucocorticoid Receptors in Human Synovial Tissue and Relative Receptor Affinities of Glucocorticoid-21-Esters
A dexamethasone binding protein was detected in cytosol of 11 human synovial tissues from patients with chronic polyarthritis and results of competition assays with an excess of unlabeled aldosterone, estradiol, pregnenolone, and testosterone confirmed that the binding protein had characteristics of a glucocorticoid receptor.
0.25% Prednicarbate cream and the corresponding vehicle induce less skin atrophy than 0.1% betamethasone-17-valerate cream and 0.05% clobetasol-17-propionate cream
Given that 0.1% betamethasone-17-valerate- and 0.25% prednicarbate cream are reported to be about equipotent in the treatment of atopic eczema the latter preparation shows an increased ratio between its desired anti-inflammatory and its unwanted atrophogenic effect.