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Tacrolimus for the treatment of primary sclerosing cholangitis
Author(s) -
Talwalkar Jayant A.,
Gossard Andrea A.,
Keach Jill C.,
Jorgensen Roberta A.,
Petz Janice L.,
Lindor R. N. Keith D.
Publication year - 2007
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2007.01441.x
Subject(s) - tacrolimus , medicine , alkaline phosphatase , primary sclerosing cholangitis , adverse effect , bilirubin , gastroenterology , calcineurin , toxicity , albumin , transplantation , biochemistry , chemistry , disease , enzyme
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. Aims: 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.