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Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients
The purpose of this study was to evaluate the effects of NR1I2 (7635G>A and 8055C>T) and ABCB1 (1236C>T, 2677G>T/A, and 3435C>T) genetic polymorphisms on everolimus pharmacokinetics in 98 Japanese renal transplant patients. On day 15 after everolimus administration, blood samples were...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570057/ https://www.ncbi.nlm.nih.gov/pubmed/36233042 http://dx.doi.org/10.3390/ijms231911742 |
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author | Yagishita, Hironobu Kagaya, Hideaki Saito, Mitsuru Numakura, Kazuyuki Yamamoto, Ryohei Sagehashi, Ryuichiro Habuchi, Tomonori Satoh, Shigeru Miura, Masatomo |
author_facet | Yagishita, Hironobu Kagaya, Hideaki Saito, Mitsuru Numakura, Kazuyuki Yamamoto, Ryohei Sagehashi, Ryuichiro Habuchi, Tomonori Satoh, Shigeru Miura, Masatomo |
author_sort | Yagishita, Hironobu |
collection | PubMed |
description | The purpose of this study was to evaluate the effects of NR1I2 (7635G>A and 8055C>T) and ABCB1 (1236C>T, 2677G>T/A, and 3435C>T) genetic polymorphisms on everolimus pharmacokinetics in 98 Japanese renal transplant patients. On day 15 after everolimus administration, blood samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after administration. The dose-adjusted area under the blood concentration–time curve (AUC(0-12)) of everolimus was significantly lower in patients with the NR1I2 8055C/C genotype than in those with other genotypes (p = 0.022) and was significantly higher in male patients than female patients (p = 0.045). Significant correlations between the dose-adjusted AUC(0-12) of everolimus and age (p = 0.001), aspartate transaminase (p = 0.001), and alanine transaminase (p = 0.005) were found. In multivariate analysis, aging (p = 0.008) and higher alanine transaminase levels (p = 0.032) were independently predictive of a higher dose-adjusted everolimus AUC(0-12). Aging and hepatic dysfunction in patients may need to be considered when evaluating dose reductions in everolimus. In renal transplant patients, management using everolimus blood concentrations after administration may be more important than analysis of NR1I2 8055C>T polymorphism before administration. |
format | Online Article Text |
id | pubmed-9570057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95700572022-10-17 Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients Yagishita, Hironobu Kagaya, Hideaki Saito, Mitsuru Numakura, Kazuyuki Yamamoto, Ryohei Sagehashi, Ryuichiro Habuchi, Tomonori Satoh, Shigeru Miura, Masatomo Int J Mol Sci Article The purpose of this study was to evaluate the effects of NR1I2 (7635G>A and 8055C>T) and ABCB1 (1236C>T, 2677G>T/A, and 3435C>T) genetic polymorphisms on everolimus pharmacokinetics in 98 Japanese renal transplant patients. On day 15 after everolimus administration, blood samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after administration. The dose-adjusted area under the blood concentration–time curve (AUC(0-12)) of everolimus was significantly lower in patients with the NR1I2 8055C/C genotype than in those with other genotypes (p = 0.022) and was significantly higher in male patients than female patients (p = 0.045). Significant correlations between the dose-adjusted AUC(0-12) of everolimus and age (p = 0.001), aspartate transaminase (p = 0.001), and alanine transaminase (p = 0.005) were found. In multivariate analysis, aging (p = 0.008) and higher alanine transaminase levels (p = 0.032) were independently predictive of a higher dose-adjusted everolimus AUC(0-12). Aging and hepatic dysfunction in patients may need to be considered when evaluating dose reductions in everolimus. In renal transplant patients, management using everolimus blood concentrations after administration may be more important than analysis of NR1I2 8055C>T polymorphism before administration. MDPI 2022-10-03 /pmc/articles/PMC9570057/ /pubmed/36233042 http://dx.doi.org/10.3390/ijms231911742 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yagishita, Hironobu Kagaya, Hideaki Saito, Mitsuru Numakura, Kazuyuki Yamamoto, Ryohei Sagehashi, Ryuichiro Habuchi, Tomonori Satoh, Shigeru Miura, Masatomo Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients |
title | Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients |
title_full | Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients |
title_fullStr | Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients |
title_full_unstemmed | Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients |
title_short | Effects of NR1I2 and ABCB1 Genetic Polymorphisms on Everolimus Pharmacokinetics in Japanese Renal Transplant Patients |
title_sort | effects of nr1i2 and abcb1 genetic polymorphisms on everolimus pharmacokinetics in japanese renal transplant patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570057/ https://www.ncbi.nlm.nih.gov/pubmed/36233042 http://dx.doi.org/10.3390/ijms231911742 |
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