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

Sakiko Hiraoka, Jun Kato, Yuki Moritou, Daisuke Takei, Toshihiro Inokuchi, Asuka Nakarai, Sakuma Takahashi, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number53
JournalBMC Gastroenterology
Volume15
Issue number1
DOIs
Publication statusPublished - Apr 29 2015

Fingerprint

Remission Induction
Tacrolimus
Ulcerative Colitis
Therapeutics
Cytochrome P-450 CYP3A
Confidence Intervals

Keywords

  • Remission
  • Single-nucleotide polymorphisms
  • Tacrolimus
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients. / Hiraoka, Sakiko; Kato, Jun; Moritou, Yuki; Takei, Daisuke; Inokuchi, Toshihiro; Nakarai, Asuka; Takahashi, Sakuma; Harada, Keita; Okada, Hiroyuki; Yamamoto, Kazuhide.

In: BMC Gastroenterology, Vol. 15, No. 1, 53, 29.04.2015.

Research output: Contribution to journalArticle

Hiraoka, Sakiko ; Kato, Jun ; Moritou, Yuki ; Takei, Daisuke ; Inokuchi, Toshihiro ; Nakarai, Asuka ; Takahashi, Sakuma ; Harada, Keita ; Okada, Hiroyuki ; Yamamoto, Kazuhide. / The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients. In: BMC Gastroenterology. 2015 ; Vol. 15, No. 1.
@article{a3cd0278bff249ffbf25f55c2633e5ac,
title = "The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients",
abstract = "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.",
keywords = "Remission, Single-nucleotide polymorphisms, Tacrolimus, Ulcerative colitis",
author = "Sakiko Hiraoka and Jun Kato and Yuki Moritou and Daisuke Takei and Toshihiro Inokuchi and Asuka Nakarai and Sakuma Takahashi and Keita Harada and Hiroyuki Okada and Kazuhide Yamamoto",
year = "2015",
month = "4",
day = "29",
doi = "10.1186/s12876-015-0285-3",
language = "English",
volume = "15",
journal = "BMC Gastroenterology",
issn = "1471-230X",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients

AU - Hiraoka, Sakiko

AU - Kato, Jun

AU - Moritou, Yuki

AU - Takei, Daisuke

AU - Inokuchi, Toshihiro

AU - Nakarai, Asuka

AU - Takahashi, Sakuma

AU - Harada, Keita

AU - Okada, Hiroyuki

AU - Yamamoto, Kazuhide

PY - 2015/4/29

Y1 - 2015/4/29

N2 - 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.

AB - 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.

KW - Remission

KW - Single-nucleotide polymorphisms

KW - Tacrolimus

KW - Ulcerative colitis

UR - http://www.scopus.com/inward/record.url?scp=84929619873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929619873&partnerID=8YFLogxK

U2 - 10.1186/s12876-015-0285-3

DO - 10.1186/s12876-015-0285-3

M3 - Article

VL - 15

JO - BMC Gastroenterology

JF - BMC Gastroenterology

SN - 1471-230X

IS - 1

M1 - 53

ER -