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Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers

A high intra-patient variability (IPV) of tacrolimus exposure is associated with poor long-term kidney transplantation outcomes. To assess the influence of cytochrome P450 (CYP) 3A5 genetic polymorphisms on tacrolimus IPV, 188 clinically stable kidney transplant recipients, who had received an immed...

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Autores principales: Nuchjumroon, Almas, Vadcharavivad, Somratai, Singhan, Wanchana, Poosoonthornsri, Manorom, Chancharoenthana, Wiwat, Udomkarnjananun, Suwasin, Townamchai, Natavudh, Avihingsanon, Yingyos, Praditpornsilpa, Kearkiat, Eiam-Ong, Somchai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658797/
https://www.ncbi.nlm.nih.gov/pubmed/36362548
http://dx.doi.org/10.3390/jcm11216320
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author Nuchjumroon, Almas
Vadcharavivad, Somratai
Singhan, Wanchana
Poosoonthornsri, Manorom
Chancharoenthana, Wiwat
Udomkarnjananun, Suwasin
Townamchai, Natavudh
Avihingsanon, Yingyos
Praditpornsilpa, Kearkiat
Eiam-Ong, Somchai
author_facet Nuchjumroon, Almas
Vadcharavivad, Somratai
Singhan, Wanchana
Poosoonthornsri, Manorom
Chancharoenthana, Wiwat
Udomkarnjananun, Suwasin
Townamchai, Natavudh
Avihingsanon, Yingyos
Praditpornsilpa, Kearkiat
Eiam-Ong, Somchai
author_sort Nuchjumroon, Almas
collection PubMed
description A high intra-patient variability (IPV) of tacrolimus exposure is associated with poor long-term kidney transplantation outcomes. To assess the influence of cytochrome P450 (CYP) 3A5 genetic polymorphisms on tacrolimus IPV, 188 clinically stable kidney transplant recipients, who had received an immediate-release tacrolimus-based immunosuppressive regimen, were enrolled in this retrospective cohort study. Genotyping of CYP3A5*3 (rs776746) was performed and 110 (58.5%) were identified as CYP3A5 expressers and 78 (41.5%) as nonexpressers. Whole blood tacrolimus concentrations were analyzed by chemiluminescent microparticle immunoassay. Dose-adjusted trough tacrolimus concentrations (C0/D) measured at months 6, 9, and 12 were used to determine IPV. There were no significant differences in the IPV estimated by the coefficient of variation, the IPV calculated by mean absolute deviation method, and the proportions of recipients with the IPV estimated by the coefficient of variation of 30% or more between CYP3A5 expressers and nonexpressers (p = 0.613, 0.686, and 0.954, respectively). Tacrolimus C0/D in CYP3A5 expressers was approximately half of those in nonexpressers, overall (p < 0.001). In both CYP3A5 expressers and nonexpressers, tacrolimus C0/D increased gradually from month 6 to month 12 (p = 0.021). There was no evidence that the CYP3A5 polymorphisms significantly influence tacrolimus IPV during the 6 to 12 months after kidney transplantation.
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spelling pubmed-96587972022-11-15 Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers Nuchjumroon, Almas Vadcharavivad, Somratai Singhan, Wanchana Poosoonthornsri, Manorom Chancharoenthana, Wiwat Udomkarnjananun, Suwasin Townamchai, Natavudh Avihingsanon, Yingyos Praditpornsilpa, Kearkiat Eiam-Ong, Somchai J Clin Med Article A high intra-patient variability (IPV) of tacrolimus exposure is associated with poor long-term kidney transplantation outcomes. To assess the influence of cytochrome P450 (CYP) 3A5 genetic polymorphisms on tacrolimus IPV, 188 clinically stable kidney transplant recipients, who had received an immediate-release tacrolimus-based immunosuppressive regimen, were enrolled in this retrospective cohort study. Genotyping of CYP3A5*3 (rs776746) was performed and 110 (58.5%) were identified as CYP3A5 expressers and 78 (41.5%) as nonexpressers. Whole blood tacrolimus concentrations were analyzed by chemiluminescent microparticle immunoassay. Dose-adjusted trough tacrolimus concentrations (C0/D) measured at months 6, 9, and 12 were used to determine IPV. There were no significant differences in the IPV estimated by the coefficient of variation, the IPV calculated by mean absolute deviation method, and the proportions of recipients with the IPV estimated by the coefficient of variation of 30% or more between CYP3A5 expressers and nonexpressers (p = 0.613, 0.686, and 0.954, respectively). Tacrolimus C0/D in CYP3A5 expressers was approximately half of those in nonexpressers, overall (p < 0.001). In both CYP3A5 expressers and nonexpressers, tacrolimus C0/D increased gradually from month 6 to month 12 (p = 0.021). There was no evidence that the CYP3A5 polymorphisms significantly influence tacrolimus IPV during the 6 to 12 months after kidney transplantation. MDPI 2022-10-26 /pmc/articles/PMC9658797/ /pubmed/36362548 http://dx.doi.org/10.3390/jcm11216320 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
Nuchjumroon, Almas
Vadcharavivad, Somratai
Singhan, Wanchana
Poosoonthornsri, Manorom
Chancharoenthana, Wiwat
Udomkarnjananun, Suwasin
Townamchai, Natavudh
Avihingsanon, Yingyos
Praditpornsilpa, Kearkiat
Eiam-Ong, Somchai
Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers
title Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers
title_full Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers
title_fullStr Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers
title_full_unstemmed Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers
title_short Comparison of Tacrolimus Intra-Patient Variability during 6–12 Months after Kidney Transplantation between CYP3A5 Expressers and Nonexpressers
title_sort comparison of tacrolimus intra-patient variability during 6–12 months after kidney transplantation between cyp3a5 expressers and nonexpressers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9658797/
https://www.ncbi.nlm.nih.gov/pubmed/36362548
http://dx.doi.org/10.3390/jcm11216320
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