Digestion
Original Paper
Tacrolimus Dose Optimization Strategy for Refractory Ulcerative Colitis Based on the Cytochrome P450 3A5 Polymorphism Prediction Using Trough Concentration after 24 HoursOnodera M.a · Endo K.b · Naito T.a · Moroi R.a · Kuroha M.a · Kanazawa Y.a · Kimura T.a · Shiga H.c · Kakuta Y.a · Negoro K.a · Kinouchi Y.d · Shimosegawa T.aaDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
bDivision of Gastroenterology and Hepatology, Tohoku Medical and Pharmaceutical University, Miyagi, Japan cDepartment of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan dHealth Administration Center, Center for the Advancement of Higher Education, Tohoku University, Miyagi, Japan |
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Article / Publication Details
Published online: February 01, 2018
Issue release date: February 2018
Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 2
ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)
For additional information: https://www.karger.com/DIG
Abstract
Background: In the tacrolimus treatment for refractory ulcerative colitis (UC), dose adjustment is necessary because the required doses to keep appropriate drug concentrations are significantly different among individuals. Cytochrome P450 (CYP) 3A5 polymorphism affects tacrolimus blood concentrations. However, it is difficult to obtain genetic information in real clinical practice. In the present study, we investigated possible factors that may predict CYP3A5 polymorphism and proposed a dose optimization strategy based on the obtained predicting factors. Summary: We retrospectively analyzed 41 patients who underwent remission induction therapy with tacrolimus for UC in our hospital. First, we performed a correlation analysis of CYP3A5 polymorphism and pharmacokinetics. In the CYP3A5 non-expressers, the dose of tacrolimus (mg/kg) was lower and dose-adjusted trough levels (ng/mL per mg/kg) were higher compared with those in expressers. Next, we investigated factors that could predict CYP3A5 polymorphism. Trough concentration 24 h following tacrolimus administration was extracted as a significant factor. When the trough cutoff value at 24 h was set to 2.6 ng/mL, sensitivity and specificity for estimation of CYP3A5 polymorphism were 63 and 96% respectively. Therefore, when the trough concentration 24 h after administration is ≤2.6 ng/mL, the patient can be estimated as a CYP3A5 expresser and an increase in dose should be proposed. Key Message: The trough concentration 24 h after the first tacrolimus administration appears to be a useful predictor of CYP3A5 polymorphism. Performing dose optimization strategy based on the prediction of CYP3A5 polymorphism can lead to earlier and safer remission induction.
© 2018 S. Karger AG, Basel
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Article / Publication Details
Published online: February 01, 2018
Issue release date: February 2018
Number of Print Pages: 7
Number of Figures: 2
Number of Tables: 2
ISSN: 0012-2823 (Print)
eISSN: 1421-9867 (Online)
For additional information: https://www.karger.com/DIG
Copyright / Drug Dosage / Disclaimer
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