CYP3A5 influences oral tacrolimus pharmacokinetics and timing of acute kidney injury following allogeneic hematopoietic stem cell transplantation.
| Title: | CYP3A5 influences oral tacrolimus pharmacokinetics and timing of acute kidney injury following allogeneic hematopoietic stem cell transplantation. |
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| Authors: | Seligson, Nathan D., Xunjie Zhang, Zemanek, Mark C., Johnson, Jasmine A., VanGundy, Zachary, Danxin Wang, Phelps, Mitch A., Roddy, Julianna, Hofmeister, Craig C., Junan Li, Poi, Ming J. |
| Source: | Frontiers in Pharmacology; 2024, p1-10, 10p |
| Subject Terms: | HEMATOPOIETIC stem cell transplantation, ACUTE kidney failure, CYTOCHROME P-450 CYP3A, TACROLIMUS, STEM cell transplantation |
| Abstract: | Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described. Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642). Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population. Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT. [ABSTRACT FROM AUTHOR] |
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| Database: | Complementary Index |
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| Items | – Name: Title Label: Title Group: Ti Data: CYP3A5 influences oral tacrolimus pharmacokinetics and timing of acute kidney injury following allogeneic hematopoietic stem cell transplantation. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Seligson%2C+Nathan+D%2E%22">Seligson, Nathan D.</searchLink><br /><searchLink fieldCode="AR" term="%22Xunjie+Zhang%22">Xunjie Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Zemanek%2C+Mark+C%2E%22">Zemanek, Mark C.</searchLink><br /><searchLink fieldCode="AR" term="%22Johnson%2C+Jasmine+A%2E%22">Johnson, Jasmine A.</searchLink><br /><searchLink fieldCode="AR" term="%22VanGundy%2C+Zachary%22">VanGundy, Zachary</searchLink><br /><searchLink fieldCode="AR" term="%22Danxin+Wang%22">Danxin Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Phelps%2C+Mitch+A%2E%22">Phelps, Mitch A.</searchLink><br /><searchLink fieldCode="AR" term="%22Roddy%2C+Julianna%22">Roddy, Julianna</searchLink><br /><searchLink fieldCode="AR" term="%22Hofmeister%2C+Craig+C%2E%22">Hofmeister, Craig C.</searchLink><br /><searchLink fieldCode="AR" term="%22Junan+Li%22">Junan Li</searchLink><br /><searchLink fieldCode="AR" term="%22Poi%2C+Ming+J%2E%22">Poi, Ming J.</searchLink> – Name: TitleSource Label: Source Group: Src Data: Frontiers in Pharmacology; 2024, p1-10, 10p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22HEMATOPOIETIC+stem+cell+transplantation%22">HEMATOPOIETIC stem cell transplantation</searchLink><br /><searchLink fieldCode="DE" term="%22ACUTE+kidney+failure%22">ACUTE kidney failure</searchLink><br /><searchLink fieldCode="DE" term="%22CYTOCHROME+P-450+CYP3A%22">CYTOCHROME P-450 CYP3A</searchLink><br /><searchLink fieldCode="DE" term="%22TACROLIMUS%22">TACROLIMUS</searchLink><br /><searchLink fieldCode="DE" term="%22STEM+cell+transplantation%22">STEM cell transplantation</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described. Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642). Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population. Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Frontiers in Pharmacology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3389/fphar.2023.1334440 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 1 Subjects: – SubjectFull: HEMATOPOIETIC stem cell transplantation Type: general – SubjectFull: ACUTE kidney failure Type: general – SubjectFull: CYTOCHROME P-450 CYP3A Type: general – SubjectFull: TACROLIMUS Type: general – SubjectFull: STEM cell transplantation Type: general Titles: – TitleFull: CYP3A5 influences oral tacrolimus pharmacokinetics and timing of acute kidney injury following allogeneic hematopoietic stem cell transplantation. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Seligson, Nathan D. – PersonEntity: Name: NameFull: Xunjie Zhang – PersonEntity: Name: NameFull: Zemanek, Mark C. – PersonEntity: Name: NameFull: Johnson, Jasmine A. – PersonEntity: Name: NameFull: VanGundy, Zachary – PersonEntity: Name: NameFull: Danxin Wang – PersonEntity: Name: NameFull: Phelps, Mitch A. – PersonEntity: Name: NameFull: Roddy, Julianna – PersonEntity: Name: NameFull: Hofmeister, Craig C. – PersonEntity: Name: NameFull: Junan Li – PersonEntity: Name: NameFull: Poi, Ming J. IsPartOfRelationships: – BibEntity: Dates: – D: 20 M: 01 Text: 2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 16639812 Titles: – TitleFull: Frontiers in Pharmacology Type: main |
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