Intest Res.  2019 Apr;17(2):218-226. 10.5217/ir.2018.00117.

Individualized treatment based on CYP3A5 single-nucleotide polymorphisms with tacrolimus in ulcerative colitis

Affiliations
  • 1Center for Advanced IBD Research and Treatment, Department of Research, Kitasato University Kitasato Institute Hospital, Tokyo, Japan. kobataku@insti.kitasato-u.ac.jp
  • 2Department of Gastroenterology and Hepatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
  • 3Department of Rheumatology, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
  • 4Department of Pharmacy, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
  • 5Biomedical Laboratory, Department of Research, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.

Abstract

BACKGROUND/AIMS
The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis.
METHODS
Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day).
RESULTS
The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group.
CONCLUSIONS
Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.

Keyword

Colitis, ulcerative; Tacrolimus; Individualized treatment; CYP3A5

MeSH Terms

Colitis, Ulcerative*
Cytochrome P-450 CYP3A*
Genotype
Humans
Pharmacokinetics
Polymorphism, Single Nucleotide
Prospective Studies
Tacrolimus*
Ulcer*
Cytochrome P-450 CYP3A
Tacrolimus
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