抄録
Calcineurin inhibitors (CNIs), such as cyclosporine A and tacrolimus, are widely used immunosuppressive agents for the prevention of post-transplantation rejection and have improved 1-year graft survival rates by up to 90%. However, CNIs can induce severe reactions, such as acute or chronic allograft nephropathy, hypertension, and neurotoxicity. Because CNIs have varied bioavailabilities, narrow therapeutic ranges, and individual propensities for toxic effects, therapeutic drug monitoring is necessary for all CNIs. Identifying the genetic polymorphisms in drug-metabolizing enzymes will help to determine personalized dosage regimens for CNIs, as CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp, MDR1). CNIs are often concomitantly administered with voriconazole or proton pump inhibitors (PPIs), giving rise to drug interaction problems. Voriconazole and PPIs can increase the blood concentrations of CNIs, and both are primarily metabolized by CYP2C19. Thus, it is expected that interactions between CNIs and voriconazole or PPI would be affected by CYP2C19 and CYP3A5 polymorphisms. CNI-induced acute kidney injury (AKI) is a serious complication of transplantations. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are noninvasive urinary biomarkers that are believed to be highly sensitive to CNI-induced AKI. In this article, we review the adverse events and pharmacokinetics of CNIs and the biomarkers related to CNIs, including CYP3A5, CYP2C19, MDR1, NGAL, and KIM-1. We hope that these data will help to identify the optimal biomarkers for monitoring CNI-based immunosuppressive therapy after organ transplantation.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 151-159 |
| ページ数 | 9 |
| ジャーナル | Acta Pharmacologica Sinica |
| 巻 | 40 |
| 発行部数 | 2 |
| DOI | |
| 出版物ステータス | 出版済み - 2 1 2019 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmacology (medical)
これを引用
Biomarkers for individualized dosage adjustments in immunosuppressive therapy using calcineurin inhibitors after organ transplantation. / Fu, Rao; Tajima, Soichiro; Suetsugu, Kimitaka; Watanabe, Hiroyuki; Egashira, Nobuaki; Masuda, Satohiro.
：: Acta Pharmacologica Sinica, 巻 40, 番号 2, 01.02.2019, p. 151-159.研究成果: ジャーナルへの寄稿 › 評論記事
}
TY - JOUR
T1 - Biomarkers for individualized dosage adjustments in immunosuppressive therapy using calcineurin inhibitors after organ transplantation
AU - Fu, Rao
AU - Tajima, Soichiro
AU - Suetsugu, Kimitaka
AU - Watanabe, Hiroyuki
AU - Egashira, Nobuaki
AU - Masuda, Satohiro
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Calcineurin inhibitors (CNIs), such as cyclosporine A and tacrolimus, are widely used immunosuppressive agents for the prevention of post-transplantation rejection and have improved 1-year graft survival rates by up to 90%. However, CNIs can induce severe reactions, such as acute or chronic allograft nephropathy, hypertension, and neurotoxicity. Because CNIs have varied bioavailabilities, narrow therapeutic ranges, and individual propensities for toxic effects, therapeutic drug monitoring is necessary for all CNIs. Identifying the genetic polymorphisms in drug-metabolizing enzymes will help to determine personalized dosage regimens for CNIs, as CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp, MDR1). CNIs are often concomitantly administered with voriconazole or proton pump inhibitors (PPIs), giving rise to drug interaction problems. Voriconazole and PPIs can increase the blood concentrations of CNIs, and both are primarily metabolized by CYP2C19. Thus, it is expected that interactions between CNIs and voriconazole or PPI would be affected by CYP2C19 and CYP3A5 polymorphisms. CNI-induced acute kidney injury (AKI) is a serious complication of transplantations. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are noninvasive urinary biomarkers that are believed to be highly sensitive to CNI-induced AKI. In this article, we review the adverse events and pharmacokinetics of CNIs and the biomarkers related to CNIs, including CYP3A5, CYP2C19, MDR1, NGAL, and KIM-1. We hope that these data will help to identify the optimal biomarkers for monitoring CNI-based immunosuppressive therapy after organ transplantation.
AB - Calcineurin inhibitors (CNIs), such as cyclosporine A and tacrolimus, are widely used immunosuppressive agents for the prevention of post-transplantation rejection and have improved 1-year graft survival rates by up to 90%. However, CNIs can induce severe reactions, such as acute or chronic allograft nephropathy, hypertension, and neurotoxicity. Because CNIs have varied bioavailabilities, narrow therapeutic ranges, and individual propensities for toxic effects, therapeutic drug monitoring is necessary for all CNIs. Identifying the genetic polymorphisms in drug-metabolizing enzymes will help to determine personalized dosage regimens for CNIs, as CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp, MDR1). CNIs are often concomitantly administered with voriconazole or proton pump inhibitors (PPIs), giving rise to drug interaction problems. Voriconazole and PPIs can increase the blood concentrations of CNIs, and both are primarily metabolized by CYP2C19. Thus, it is expected that interactions between CNIs and voriconazole or PPI would be affected by CYP2C19 and CYP3A5 polymorphisms. CNI-induced acute kidney injury (AKI) is a serious complication of transplantations. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are noninvasive urinary biomarkers that are believed to be highly sensitive to CNI-induced AKI. In this article, we review the adverse events and pharmacokinetics of CNIs and the biomarkers related to CNIs, including CYP3A5, CYP2C19, MDR1, NGAL, and KIM-1. We hope that these data will help to identify the optimal biomarkers for monitoring CNI-based immunosuppressive therapy after organ transplantation.
UR - http://www.scopus.com/inward/record.url?scp=85049115972&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049115972&partnerID=8YFLogxK
U2 - 10.1038/s41401-018-0070-2
DO - 10.1038/s41401-018-0070-2
M3 - Review article
VL - 40
SP - 151
EP - 159
JO - Zhongguo yao li xue bao = Acta pharmacologica Sinica
JF - Zhongguo yao li xue bao = Acta pharmacologica Sinica
SN - 1671-4083
IS - 2
ER -