title: Pharmacokinetics, efficacy and safety of alitretinoin in moderate or severe chronic hand eczema.
abstract: BACKGROUND
  Recent studies have found that alitretinoin can induce clinically significant responses in subjects with severe chronic hand eczema (CHE) unresponsive to topical corticosteroids.
  
  
  OBJECTIVE
  To assess the pharmacokinetics (PK), efficacy and safety of alitretinoin 10 or 30 mg once daily.
  
  
  METHODS
  This was a randomized, double-blind study, which enrolled 32 subjects aged 18-75 years with CHE unresponsive to potent topical corticosteroids. Subjects received alitretinoin 10 mg (n = 16) or 30 mg (n = 16) once daily for 12 or 24 weeks. Standard PK variables [area under the curve (AUC) of plasma concentration vs. time, maximum plasma concentration (C(max)), time to maximum plasma concentration (t(max)), elimination half-life (t(1/2)), total systemic clearance (CL/F) and volume of distribution (Vd/F)] were determined for alitretinoin and metabolites. Efficacy was assessed using the Physician's Global Assessment (PGA) scale.
  
  
  RESULTS
  Chronic administration of alitretinoin for up to 24 weeks did not result in accumulation or time-dependent changes in the disposition of alitretinoin. Exposure was found to be proportional to dose. Systemic exposure (AUC) to alitretinoin was proportional to dose for 10 and 30 mg alitretinoin; 62.8% of subjects achieved clear/almost clear hands in the 30 mg group and 12.5% in the 10 mg group. Alitretinoin was well tolerated.
  
  
  CONCLUSIONS
  Chronic administration of alitretinoin for 12-24 weeks did not lead to accumulation or time-dependent changes in drug exposure. Alitretinoin was effective and well tolerated in the treatment of subjects with moderate or severe CHE unresponsive to potent topical corticosteroids.
authors: Basilea Pharmaceutica International Ltd, Basel, Switzerland. anne.schmitt-hoffmann@basilea.com
authors: A H
authors: AH
authors: Schmitt-Hoffmann
authors: B
authors: B
authors: Roos
authors: J
authors: J
authors: Sauer
authors: J
authors: J
authors: Spickermann
authors: K
authors: K
authors: Stoeckel
authors: D
authors: D
authors: Edwards
authors: J
authors: J
authors: van de Wetering
authors: P J
authors: PJ
authors: Coenraads
authors: J
authors: J
authors: Maares
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000077556:Alitretinoin; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006229:Hand Dermatoses / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014212:Tretinoin / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D000077556:Alitretinoin; D014212:Tretinoin