- IBD
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Individualized treatment based on CYP3A5 single-nucleotide polymorphisms with tacrolimus in ulcerative colitis
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Shinji Okabayashi, Taku Kobayashi, Eiko Saito, Takahiko Toyonaga, Ryo Ozaki, Shintaro Sagami, Masaru Nakano, Junichi Tanaka, Keiji Yagisawa, Satoshi Kuronuma, Osamu Takeuchi, Toshifumi Hibi
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Intest Res 2019;17(2):218-226. Published online February 7, 2019
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DOI: https://doi.org/10.5217/ir.2018.00117
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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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Citations
Citations to this article as recorded by  - The impact of cytochrome P450 3A genetic polymorphisms on tacrolimus pharmacokinetics in ulcerative colitis patients
Maizumi Furuse, Shuhei Hosomi, Yu Nishida, Shigehiro Itani, Yuji Nadatani, Shusei Fukunaga, Koji Otani, Fumio Tanaka, Yasuaki Nagami, Koichi Taira, Noriko Kamata, Toshio Watanabe, Kenji Watanabe, Yasuhiro Fujiwara, Erika Cecchin
PLOS ONE.2021; 16(4): e0250597. CrossRef - Advances in research of tacrolimus for treatment of inflammatory bowel disease
Jing-Jing Wang, Yi-Hong Fan
World Chinese Journal of Digestology.2019; 27(13): 842. CrossRef
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