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Präklinische Validierung der Sicherheit von Chloralhydrat zur topischen Applikation am Beispiel des psoriatischen Pruritus

Preclinical safety evaluation of chloral hydrate after topical application using the example of psoriatic itch

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Zusammenfassung

Hintergrund

Die Psoriasis wird heute als T‑Zell vermittelte autoimmunologische Systemerkrankung verstanden. Das chronisch entzündliche Geschehen bezieht auch neuroimmunologische Faktoren ein, die nicht nur für verschiedene Fassetten einer psychiatrisch-neurologischen Komorbidität, sondern auch für neurosensorische Symptome, allen voran den Pruritus verantwortlich gemacht werden. Unter anderem wird in diesem Zusammenhang die Bedeutung von GABAA-Rezeptoren diskutiert. Die topische Anwendung in halbfesten Zubereitungen zur antipruriginösen Therapie geht auf Neisser zurück und erfährt derzeit eine Renaissance in der magistralen Rezeptur. Bisher ist allerdings unbekannt, ob die aus der systemischen Anwendung von Chloralhydrat bekannten unerwünschten Wirkungen auch für die topische Anwendung praktische Relevanz besitzen.

Zielsetzung

Aus Mangel an klinischen Sicherheitsdaten zur topischen Anwendung wurden präklinische Untersuchungen zur kutanen Zytotoxizität, zur kutanen Verträglichkeit und Berechnungen zur systemischen Bioverfügbarkeit nach topischer Applikation vorgenommen.

Ergebnisse

Zusammenfassend kann festgestellt werden, dass die erarbeiteten Daten relevante Sicherheitsbedenken bei kontrollierter Applikation von Chloralhydrat mit der favorisierten Rezeptur aus dem Neues Rezepturformularium (NRF) (sog. 1‑2-3-Creme) nicht vollständig ausräumen können. Eine Anwendung der 1‑2-3-Creme bei maximal 2‑mal täglicher Applikation auf bis zu 10 % der Körperoberfläche kann aber als unproblematisch angesehen werden. Um darüber hinaus eine verbesserte Bewertung der Unbedenklichkeit zu erreichen, wären die Untersuchung der kutanen Bioverfügbarkeit (Konzentrations-Zeit-Profil) von Chloralhydrat nach epikutaner Applikation an Humanhaut bzw. klinische Studien notwendig.

Abstract

Background

Psoriasis is known today as a T‑cell-mediated autoimmunological systemic disease. The chronic inflammatory processes involve neuroimmunological factors that are held responsible not only for various aspects of psychiatric–neurological comorbidities but also for neurosensory problems, primarily itching. Amongst other things, the significance of GABAA receptors are often discussed in this context. The topical use of chloral hydrate in semisolid preparations for antipruritic therapy goes back to Neisser and is currently experiencing a revival in individually manufactured formulations. However, it is currently unknown whether the unwanted side effects that are described for systemic use of chloral hydrate are also relevant for topical application.

Objectives

For lack of clinical safety data, preclinical tests for cutaneous cytotoxicity and calculations for systemic bioavailability after topical application have been performed.

Conclusion

The present data cannot fully remove safety concerns for topical application of chloral hydrate in the formulation favoured by the NRF (Neues Rezepturformularium)—the so-called 1‑2-3-cream. A twice daily use of the 1‑2-3-cream on a maximum of 10% of the body surface can be regarded as safe. For a better assessment of harmlessness, tests for cutaneous bioavailability (concentration–time profile) on human skin and clinical studies would be necessary.

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Danksagung

Die Autoren bedanken sich bei Frau Sylke Fasshauer und Frau Claudia Bruhne für die exzellente technische Assistenz und bei Frau Dr. Julia Michael für Hinweise zur Berechnung der Bioverfügbarkeit.

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Authors and Affiliations

  1. Universitätsklinik und Poliklinik für Dermatologie und Venerologie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle (Saale), Deutschland

    J. Wohlrab, L. Wolff & M. Fischer

  2. An-Institut für angewandte Dermatopharmazie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Deutschland

    J. Wohlrab & F. Gilbrich

  3. Klinik für Dermatologie und Allergologie, Charité Universitätsmedizin Berlin, Berlin, Deutschland

    S. Philipp

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Correspondence to J. Wohlrab.

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J. Wohlrab, F. Gilbrich, L. Wolff, M. Fischer und S. Philipp geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Wohlrab, J., Gilbrich, F., Wolff, L. et al. Präklinische Validierung der Sicherheit von Chloralhydrat zur topischen Applikation am Beispiel des psoriatischen Pruritus. Hautarzt 68, 217–223 (2017). https://doi.org/10.1007/s00105-016-3909-9

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