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KMID : 0988920190170020218
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Intestinal Research
2019 Volume.17 No. 2 p.218 ~ p.226
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Individualized treatment based on CYP3A5 single-nucleotide polymorphisms with tacrolimus in ulcerative colitis
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Okabayashi Shinji
Kobayashi Taku
Saito Eiko
Toyonaga Takahiko
Ozaki Ryo
Sagami Shintaro
Nakano Masaru
Tanaka Junichi
Yagisawa Keiji
Kuronuma Satoshi
Takeuchi Osamu
Hibi Toshifumi
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Abstract
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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.
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KEYWORD
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Colitis, ulcerative, Tacrolimus, Individualized treatment, CYP3A5
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