The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients

BMC Gastroenterology

Kazuhide Yamamoto¹  Hiroyuki Okada¹  Keita Harada¹  Sakuma Takahashi¹  Asuka Nakarai¹  Toshihiro Inokuchi¹  Daisuke Takei¹  Yuki Moritou¹  Jun Kato²  Sakiko Hiraoka¹ 

[1] Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan;Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

关键词: Remission;    Single-nucleotide polymorphisms;    Tacrolimus;    Ulcerative colitis;   

Others  :  1211535
DOI  :  10.1186/s12876-015-0285-3

 received in 2014-12-28, accepted in 2015-04-20,  发布年份 2015

【 摘 要 】

Background

Oral tacrolimus therapy is effective for refractory ulcerative colitis (UC), but dose adjustment according to the trough concentrations which varies largely among individuals, is required. This study aimed to identify factors to predict the tacrolimus dose required for achieving the target trough level for remission induction of UC.

Methods

Forty-seven consecutive UC patients who were treated with tacrolimus were retrospectively analyzed. Tacrolimus doses were adjusted every 2 or 3 days to achieve trough concentrations of 10–15 ng/mL. The dose required for reaching the target trough level was analyzed based on disease characteristics, course of trough concentrations, and gene polymorphism related to tacrolimus metabolism.

Results

Median daily dose of tacrolimus required for achieving the target trough level was 0.19 (0.07-0.42) mg/kg, and patients were divided into high or low dose group (< 0.2 mg/kg or > 0.2 mg/kg). The value of initial trough concentration/starting dose was higher in the low dose group than in the high dose group (1.35 ng/mL/mg vs. 0.78 ng/mL/mg, p < 0.0001). Although presence of CYP3A5 *1 was more frequently observed in the high dose group, initial trough concentration was the only significant factor for determining requirement of high dose of tacrolimus (OR = 28.0, 95% confidence interval 3.20 – 631).

Conclusions

The most practical predictor of the dose required for achieving the target trough concentration was the trough concentration measured 2 or 3 days after starting tacrolimus therapy. Our findings would make tarcolimus administration for UC safer, easier and more effective.

【 授权许可】

   
2015 Hiraoka et al.; licensee BioMed Central.

【 图 表 】

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