caa a22 4500 477126758 CHVBK 20180405111652.0 cr unu---uuuuu 170330e19971201xx s 000 0 eng 10.1023/A:1012183914011 doi (NATIONALLICENCE)springer-10.1023/A:1012183914011 Prednicarbate Versus Conventional Topical Glucocorticoids: Pharmacodynamic Characterization In Vitro [Elektronische Daten] [Katharina Lange, Anja Gysler, Michael Bader, Burkhard Kleuser, Hans Korting, Monika Schäfer-Korting] Purpose. Pharmacodynamic characterization of topical glucocorticoids as prednicarbate (PC), its metabolites prednisolone 17-ethylcarbonate (PEC) and prednisolone (PD), betamethasone 17-valerate (BMV), beta-methasone (BM) and desoximetasone (DM) by evaluating their effects on epidermal and dermal cells. Synopsis of pharmacokinetic and pharmacodynamic studies, possibly explaining the improved benefit-risk ratio of prednicarbate. Methods. Isolated foreskin keratinocytes were used to investigate the influence on epidermal inflammatory processes, dermal fibroblasts of the same origin to study antiproliferative activities of glucocorticoids. Interleukins were measured by ELISA-assay, the influence on II-lα-production also on mRNA-level by RNAse protection assay. Proliferation was assessed by 3H thymidine incorporation and biodegradation by HPLC/UV-absorption. Cell viability was controlled by MTT assay. Results. In keratinocytes, inflammation was induced by TNFα, resulting in an increased II- lα synthesis. This cytokine was particularly suppressed by PC and BMV, whereas PEC, PD, DM and BM were less potent (p ≤ 0.05). Since, however, the double ester PC is rapidly degraded in keratinocytes, a RNAse-protection assay of II-1α mRNA was performed allowing short incubation times and thus minimizing biodegradation effects. In agreement with the previous experiment, the antiinflammatory potency of native PC was confirmed. In fibroblasts, II-lα and II-6 synthesis indicate proliferation and inflammation respectively. Whereas PC inhibited II- lα and II-6 production in fibroblasts to a minor extent only, it was strongly reduced by the conventional glucocorticoids and PEC (p ≤ 0.05). The minor unwanted effect of PC on fibroblasts was also reflected by its low influence on cell proliferation as assayed by 3H thymindine incorporation. More pronounced antiproliferative features were observed with BM, PEC and espectially BMV. Conclusions. Correlating antiphlogistic effects in keratinocytes (suppression of II-lα) with antiproliferative effects in fibroblasts (suppression of II-lα and II-6), 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. Plenum Publishing Corporation, 1997 topical glucocorticoids nationallicence keratinocytes nationallicence fibroblasts nationallicence interleukins nationallicence benefit-risk ratio nationallicence Lange Katharina Institut für Pharmazie II, Abteilung Pharmakologie und Toxikologie Freie Universität Berlin, Königin-Luise-Straβe 2+4, D-14195, Berlin aut Gysler Anja Institut für Pharmazie II, Abteilung Pharmakologie und Toxikologie Freie Universität Berlin, Königin-Luise-Straβe 2+4, D-14195, Berlin aut Bader Michael Max-Delbrück-Centrum für Molekulare Medizin, Franz-Gross-Haus 134D, Wiltbergstraβe 50, D-13122, Berlin-Buch aut Kleuser Burkhard Institut für Pharmazie II, Abteilung Pharmakologie und Toxikologie Freie Universität Berlin, Königin-Luise-Straβe 2+4, D-14195, Berlin aut Korting Hans Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Frauenlobstraβe 9-11, D-80337 München aut Schäfer-Korting Monika Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Frauenlobstraβe 9-11, D-80337 München aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1744-1749 0724-8741 14:12<1744 1997 14 11095 https://doi.org/10.1023/A:1012183914011 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012183914011 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lange Katharina Institut für Pharmazie II, Abteilung Pharmakologie und Toxikologie Freie Universität Berlin, Königin-Luise-Straβe 2+4, D-14195, Berlin aut NATIONALLICENCE 700 1- Gysler Anja Institut für Pharmazie II, Abteilung Pharmakologie und Toxikologie Freie Universität Berlin, Königin-Luise-Straβe 2+4, D-14195, Berlin aut NATIONALLICENCE 700 1- Bader Michael Max-Delbrück-Centrum für Molekulare Medizin, Franz-Gross-Haus 134D, Wiltbergstraβe 50, D-13122, Berlin-Buch aut NATIONALLICENCE 700 1- Kleuser Burkhard Institut für Pharmazie II, Abteilung Pharmakologie und Toxikologie Freie Universität Berlin, Königin-Luise-Straβe 2+4, D-14195, Berlin aut NATIONALLICENCE 700 1- Korting Hans Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Frauenlobstraβe 9-11, D-80337 München aut NATIONALLICENCE 700 1- Schäfer-Korting Monika Dermatologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, Frauenlobstraβe 9-11, D-80337 München aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/12(1997-12-01), 1744-1749 0724-8741 14:12<1744 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer