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Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation

While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-releas...

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Autores principales: Niioka, Takenori, Kagaya, Hideaki, Saito, Mitsuru, Inoue, Takamitsu, Numakura, Kazuyuki, Habuchi, Tomonori, Satoh, Shigeru, Miura, Masatomo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307337/
https://www.ncbi.nlm.nih.gov/pubmed/25594874
http://dx.doi.org/10.3390/ijms16011840
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author Niioka, Takenori
Kagaya, Hideaki
Saito, Mitsuru
Inoue, Takamitsu
Numakura, Kazuyuki
Habuchi, Tomonori
Satoh, Shigeru
Miura, Masatomo
author_facet Niioka, Takenori
Kagaya, Hideaki
Saito, Mitsuru
Inoue, Takamitsu
Numakura, Kazuyuki
Habuchi, Tomonori
Satoh, Shigeru
Miura, Masatomo
author_sort Niioka, Takenori
collection PubMed
description While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78–1.17) vs. 0.59 (0.45–0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.
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spelling pubmed-43073372015-02-02 Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation Niioka, Takenori Kagaya, Hideaki Saito, Mitsuru Inoue, Takamitsu Numakura, Kazuyuki Habuchi, Tomonori Satoh, Shigeru Miura, Masatomo Int J Mol Sci Article While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78–1.17) vs. 0.59 (0.45–0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information. MDPI 2015-01-14 /pmc/articles/PMC4307337/ /pubmed/25594874 http://dx.doi.org/10.3390/ijms16011840 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Niioka, Takenori
Kagaya, Hideaki
Saito, Mitsuru
Inoue, Takamitsu
Numakura, Kazuyuki
Habuchi, Tomonori
Satoh, Shigeru
Miura, Masatomo
Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation
title Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation
title_full Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation
title_fullStr Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation
title_full_unstemmed Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation
title_short Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation
title_sort capability of utilizing cyp3a5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307337/
https://www.ncbi.nlm.nih.gov/pubmed/25594874
http://dx.doi.org/10.3390/ijms16011840
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