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

• Published in: Orphanet journal of rare diseases Vol. 13; no. 1; pp. 193 - 5
• Main Authors: Ablinger, Michael, Felder, Thomas K., Wimmer, Monika, Zauner, Roland, Hofbauer, Peter, Lettner, Thomas, Wolkersdorfer, Martin, Lagler, Florian B., Diem, Anja, Bauer, Johann W., Wally, Verena
• Format: Journal Article
• Language: English
• Published: London BioMed Central 01.11.2018; BioMed Central Ltd; BMC
• Subjects: Administration, Topical; Analysis; Anthraquinones - administration & dosage; Anthraquinones - chemistry; Anthraquinones - pharmacokinetics; Anthraquinones - therapeutic use; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacokinetics; Anti-Inflammatory Agents - therapeutic use; Clinical trials; Diacerein; Drug therapy; Epidermolysis bullosa; Epidermolysis Bullosa Simplex - drug therapy; Experiments; Genetic transformation; Human Genetics; Humans; Keratin; Letter to the Editor; Male; Medical research; Medicine; Medicine & Public Health; Molecular Structure; Mutation; Patient outcomes; Pediatric research; Pediatrics; Pharmacokinetics; Pharmacology/Toxicology; Rare diseases; Rare skin diseases; Skin; Topical application; Treatment outcome; Urine; Wounding; Keratin; Topical application; Epidermolysis bullosa; Pharmacokinetics; Diacerein
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-018-0940-1

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.