title: Tacrolimus for the treatment of primary sclerosing cholangitis.
abstract: BACKGROUND
  Results from a pilot investigation with tacrolimus for primary sclerosing cholangitis (PSC) demonstrated biochemical improvement without excessive drug toxicity. To date, no confirmatory study has been performed.
  
  
  OBJECTIVE
  We sought to determine the safety and efficacy of tacrolimus in PSC.
  
  
  METHODS
  An open-label, phase II study of tacrolimus 0.05 mg/kg twice daily for 1 year was performed. Target whole-blood concentrations ranged between 3 and 7 ng/ml.
  
  
  RESULTS
  A total of 16 patients were enrolled. The median age was 50 years (range, 28-68), with 31% being women. The median serum alkaline phosphatase was 903 U/l, AST 88 U/l, total bilirubin 0.9 mg/dl, and albumin 3.8 g/dl. Based primarily on drug-related adverse events, only eight (50%) patients completed 1 year of therapy. After 1 year of therapy, however, significant improvements in median serum alkaline phosphatase (903 vs. 483, P=0.0001) and AST levels (88 vs. 78, P=0.002) were observed in these patients. The median tacrolimus level in patients completing 1 year of therapy was 4.0 ng/ml. Drug-related adverse events, however, were responsible for 31% of participants withdrawing from the study.
  
  
  CONCLUSIONS
  Despite significant improvements in serum alkaline phosphatase, oral tacrolimus is poorly tolerated in patients with PSC.
authors.affiliation: Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. talwalkar.jayant@mayo.edu
authors.forename: Jayant A
authors.initials: JA
authors.lastname: Talwalkar
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Gossard
authors.forename: Jill C
authors.initials: JC
authors.lastname: Keach
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Jorgensen
authors.forename: Janice L
authors.initials: JL
authors.lastname: Petz
authors.forename: R N Keith D
authors.initials: RN
authors.lastname: Lindor
mesh_terms: D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000032:analysis; D015209:Cholangitis, Sclerosing / Q000188:drug therapy*; D004796:Clinical Enzyme Tests; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D010865:Pilot Projects; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001663:Bilirubin; D016559:Tacrolimus