title: The single-dose pharmacokinetics of alitretinoin and its metabolites are not significantly altered in patients with cirrhosis.
abstract: BACKGROUND
  Alitretinoin (9-cis-retinoic acid, Toctino(®) ) has been marketed recently for oral therapy for chronic hyperkeratotic hand eczema. As alitretinoin is highly lipophilic and metabolized mainly in the liver, it is currently considered to be contraindicated in patients with liver disease. However, the pharmacokinetics and metabolism of alitretinoin have not been studied in these patients.
  
  
  OBJECTIVE
  To study the single-dose pharmacokinetics and metabolism of alitretinoin and its metabolites in patients with cirrhosis following oral administration.
  
  
  METHODS
  Eight patients with cirrhosis and eight matched volunteer healthy controls were given a single 30-mg oral dose of alitretinoin. Blood and urine samples were collected during the following 24-h study period. Samples were analysed for alitretinoin and for known metabolites using reverse-phase high-performance liquid chromatography. The pharmacokinetics were then evaluated using standard noncompartmental models.
  
  
  RESULTS
  No significant differences were found between healthy controls and patients with cirrhosis when analysing the pharmacokinetic parameters of alitretinoin and its metabolites. Thus, the mean half-lives of alitretinoin were 5·3 and 5·6 h (P = 0.733) and the oral clearances were 1·92 and 1·39 L h(-1) kg(-1) (P = 0·243) in the patient group and the healthy control group, respectively.
  
  
  CONCLUSIONS
  The metabolism and pharmacokinetics of alitretinoin following oral administration of the recommended dose of 30 mg for the treatment of severe hand eczema were similar in patients with cirrhosis and in healthy controls. If indicated, alitretinoin can be used in these patients with careful and close monitoring.
authors.affiliation: Department of Dermato-allergology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
authors.forename: J P
authors.initials: JP
authors.lastname: Thyssen
authors.forename: L
authors.initials: L
authors.lastname: Vester
authors.forename: C
authors.initials: C
authors.lastname: Grønhøj Larsen
authors.forename: K
authors.initials: K
authors.lastname: Smidt
authors.forename: P
authors.initials: P
authors.lastname: Jakobsen
authors.forename: S H
authors.initials: SH
authors.lastname: Hansen
authors.forename: D
authors.initials: D
authors.lastname: Vind-Kezunovic
authors.forename: L L
authors.initials: LL
authors.lastname: Gluud
authors.forename: F
authors.initials: F
authors.lastname: Grønhøj Larsen
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000077556:Alitretinoin; D019540:Area Under Curve; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004485:Eczema / Q000188:drug therapy; D005260:Female; D006229:Hand Dermatoses / Q000188:drug therapy; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014212:Tretinoin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D003879:Dermatologic Agents; D000077556:Alitretinoin; D014212:Tretinoin