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Orphanet J Rare Dis. 2018 Nov 1;13(1):193. doi: 10.1186/s13023-018-0940-1.

Basal pharmacokinetic parameters of topically applied diacerein in pediatric patients with generalized severe epidermolysis bullosa simplex.

Author information

1
EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical University Salzburg, Muellner Hauptstrasse 48, 5020, Salzburg, Austria.
2
Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria.
3
Landesapotheke Salzburg, Department of Production, Hospital Pharmacy, Salzburg, Austria.
4
Institute for Inborn Errors of Metabolism and Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
5
Department of Dermatology, University Hospital Salzburg of the Paracelsus Medical University Salzburg, Salzburg, Austria.
6
EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical University Salzburg, Muellner Hauptstrasse 48, 5020, Salzburg, Austria. v.wally@salk.at.

Abstract

Generalized severe epidermolysis bullosa simplex (EBS-gen sev) is caused by mutations within either the KRT5 or KRT14 gene, phenotypically resulting in blistering and wounding of the skin and mucous membranes after minor mechanical friction. In a clinical phase 2/3 trial, diacerein has recently been shown to significantly reduce blister numbers upon topical application. In this study we addressed basic pharmacokinetic parameters of locally applied diacerein in vitro and in vivo. Ex vivo experiments using a Franz diffusion cell confirmed the uptake and bio-transformation of diacerein to rhein in a porcine skin model. Rhein, the active metabolite of diacerein, was also detected in both urine and serum samples of two EBS-gen sev patients who topically applied a 1% diacerein ointment over a period of 4 weeks. The accumulated systemic levels of rhein in EBS-gen sev patients were lower than reported levels after oral application. These preliminary findings point towards the uptake and prolonged persistance of diacerein / rhein within the intended target organ - the skin. Further, they imply an acceptable safety profile at the systemic level. TRIAL REGISTRATION: DRKS. DRKS00005412 . Registered 6 November 2013.

KEYWORDS:

Diacerein; Epidermolysis bullosa; Keratin; Pharmacokinetics; Topical application

PMID:
30382914
PMCID:
PMC6211505
DOI:
10.1186/s13023-018-0940-1
[Indexed for MEDLINE]
Free PMC Article

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