caa a22 4500 475818091 CHVBK 20180406123814.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s002280050705 doi (NATIONALLICENCE)springer-10.1007/s002280050705 Pharmacokinetics and pharmacodynamics of the novel H1-receptor antagonist emedastine in healthy volunteers [Elektronische Daten] [B. Jansen, U. Graselli, S. Dallinger, B. Kiss, V. Wacheck, H. Schlagbauer-Wadl, A. Assandri, M. Müller] Objective: Emedastine is a novel H1-receptor antagonist with pre-clinically well-documented anti-allergic effects. Here, we set out to study the relationship between emedastine pharmacokinetics and the suppressive effect on histamine-induced wheals and flares, and to compare these effects to placebo and cetirizine. Methods: Emedastine (4 mg q.d.), emedastine (2 mg b.i.d.), cetirizine (10 mg q.d.) and placebo were administered to healthy volunteers in a double-blind, cross-over fashion. On day 1 and day 5 (steady state) following drug administration, wheals and flares were induced by skin-prick testing with 1 mg ml−1 or 10 mg ml−1 histamine. Results: Following the administration of 4 mg emeda- stine q.d., mean area under the concentration-time curve (AUC)0-24 values of 34.49 ± 24.07 ng h ml−1 and 47.05 ± 36.12 ng h ml−1 were attained on day 1 and day 5, respectively. Following the administration of emedastine (2 mg b.i.d.) mean AUC0-24 values were 29.75 ± 19.92 ng h ml−1 and 46.13 ± 38.50 ng h ml−1 on day 1 and day 5, respectively. Histamine-induced wheals and flares were significantly more effectively suppressed by emedastine and cetirizine than placebo. At pharmacokinetic steady-state levels, no significant difference could be found in the potency between cetirizine and emedastine (2 mg b.i.d.). Conclusion: Emedastine displays pharmacodynamic properties comparable with cetirizine and therefore qualifies as a safe and alternative compound with H1-receptor antagonist properties. Additional larger studies may be needed to substantiate potential benefits of cetirizine over emedastine after single-dose administration. Springer-Verlag Berlin Heidelberg, 2000 Key words Emedastine nationallicence Flares nationallicence Histamine nationallicence Jansen B. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut Graselli U. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut Dallinger S. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut Kiss B. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut Wacheck V. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut Schlagbauer-Wadl H. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut Assandri A. Cross SA, Via F.A. Giorgioli, 6864 Arzo, Switzerland, CH aut Müller M. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut https://doi.org/10.1007/s002280050705 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050705 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jansen B. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut NATIONALLICENCE 700 1- Graselli U. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut NATIONALLICENCE 700 1- Dallinger S. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut NATIONALLICENCE 700 1- Kiss B. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut NATIONALLICENCE 700 1- Wacheck V. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut NATIONALLICENCE 700 1- Schlagbauer-Wadl H. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut NATIONALLICENCE 700 1- Assandri A. Cross SA, Via F.A. Giorgioli, 6864 Arzo, Switzerland, CH aut NATIONALLICENCE 700 1- Müller M. Department of Clinical Pharmacology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria e-mail: markus.mueller@univie.ac.at Tel.: +43-140-4002981; Fax: +43-140-4002998, AT aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer