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Clin Pharmacol Ther. 2011 Mar;89(3):422-8. doi: 10.1038/clpt.2010.348. Epub 2011 Feb 2.

ABCB1 single-nucleotide polymorphisms determine tacrolimus response in patients with ulcerative colitis.

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1
Department of Gastroenterology, Hepatology and Endocrinology, Robert-Bosch-Hospital, Stuttgart, Germany. klaus.herrlinger@rbk.de

Abstract

Tacrolimus (Tac) is effective in the treatment of steroid-refractory ulcerative colitis (UC); however, nonresponse and unpredictable side effects are major limitations. Because Tac response in patients who have undergone solid-organ transplantation has been associated with the presence of variants in CYP3A and ABCB1, we elucidated the contributions of CYP3A4*1B and CYP3A5*3 and of ABCB1 1236C>T, 2677G>T,A, and 3435C>T polymorphisms to Tac response in 89 patients with UC. Short-term remission and response were achieved in 61 and 14% of the patients, respectively, and were associated with colectomy-free survival. In a linear logistic regression model, patients with homozygous variants for one of the three ABCB1 alleles showed significantly higher short-term remission rates as compared with those of other genotypes. The effects held true after multivariate analysis including multiple comparisons and were more pronounced after correction for dose-adjusted Tac blood trough levels. We suggest that ABCB1, but not CYP3A5, may predict short-term remission of Tac in steroid-refractory UC.

PMID:
21289623
DOI:
10.1038/clpt.2010.348
[Indexed for MEDLINE]
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