caa a22 4500 477125727 CHVBK 20180405111648.0 cr unu---uuuuu 170330e19970601xx s 000 0 eng 10.1023/A:1012162708675 doi (NATIONALLICENCE)springer-10.1023/A:1012162708675 Prednicarbate Biotransformation in Human Foreskin Keratinocytes and Fibroblasts [Elektronische Daten] [Anja Gysler, Katharina Lange, Hans Korting, Monika Schäfer-Korting] Purpose. Evaluation of skin layer-specific prednicarbate (PC) biotransformation, possibly explaining the improved benefit/risk ratio of this topical corticosteroid in atopic dermatitis (1,2). Methods. Metabolism of PC in keratinocyte and fibroblast monolayers derived from human juvenile foreskin was evaluated. Drug concentration was determined by HPLC/UV-absorption. Accompanying cell viability tests (MTT-tests) were performed to exclude toxic drug effects. Results. Keratinocytes hydrolyzed the double ester PC (2.5 × 10−6 M) at position 21 to the monoester prednisolone 17-ethylcarbonate (P17EC) which nonenzymatically transformed to prednisolone 21-ethylcarbonate (P21EC). This metabolite was enzymatically cleaved to prednisolone (PD), the main biotransformation product at 24 hours. Fibroblasts, however, showed a distinctively lower enzyme activity. Both, PC and P17EC (or rather P21EC) were hydrolyzed to a minor extent only. The biotransformation pathway, however, was the same. When P17EC was added separately, it transformed to P21EC and again was cleaved by keratinocytes to a much higher extent. Despite of the rather high glucocorticoid concentration MTT-tests proved a non-disturbed cell viability and proliferation rate. Conclusions. Extrapolating our 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. Since skin atrophy is less pronounced with PC as compared to conventional halogenated glucocorticoids, less potent PC metabolites appear to be the dominant species in the dermis. Plenum Publishing Corporation, 1997 prednicarbate nationallicence topical glucocorticoids nationallicence pharmacokinetics nationallicence biotransformation nationallicence keratinocytes nationallicence fibroblasts nationallicence Gysler Anja Institut für Pharmazie II, Abteilung für Pharmakologie und Toxikologie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany aut Lange Katharina Institut für Pharmazie II, Abteilung für Pharmakologie und Toxikologie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany aut Korting Hans Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-, Universität, Frauenlobstr. 9-11, 80337, München, Germany aut Schäfer-Korting Monika Institut für Pharmazie II, Abteilung für Pharmakologie und Toxikologie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 793-797 0724-8741 14:6<793 1997 14 11095 https://doi.org/10.1023/A:1012162708675 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012162708675 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gysler Anja Institut für Pharmazie II, Abteilung für Pharmakologie und Toxikologie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Lange Katharina Institut für Pharmazie II, Abteilung für Pharmakologie und Toxikologie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Korting Hans Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-, Universität, Frauenlobstr. 9-11, 80337, München, Germany aut NATIONALLICENCE 700 1- Schäfer-Korting Monika Institut für Pharmazie II, Abteilung für Pharmakologie und Toxikologie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195, Berlin, Germany aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/6(1997-06-01), 793-797 0724-8741 14:6<793 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer