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
N1 - Publisher Copyright:
© 2015 Hiraoka et al.
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
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U2 - 10.1186/s12876-015-0285-3
DO - 10.1186/s12876-015-0285-3
M3 - Article
C2 - 25925267
AN - SCOPUS:84929619873
SN - 1471-230X
VL - 15
JO - BMC Gastroenterology
JF - BMC Gastroenterology
IS - 1
M1 - 53
ER -