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Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics

The influence of pharmacogenetics in tacrolimus pharmacokinetics and pharmacodynamics needs further investigation, considering its potential in assisting clinicians to predict the optimal starting dosage and the need for a personalized adjustment of the dose, as well as to identify patients at a hig...

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Autores principales: Brunet, Mercè, Pastor-Anglada, Marçal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503558/
https://www.ncbi.nlm.nih.gov/pubmed/36145503
http://dx.doi.org/10.3390/pharmaceutics14091755
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author Brunet, Mercè
Pastor-Anglada, Marçal
author_facet Brunet, Mercè
Pastor-Anglada, Marçal
author_sort Brunet, Mercè
collection PubMed
description The influence of pharmacogenetics in tacrolimus pharmacokinetics and pharmacodynamics needs further investigation, considering its potential in assisting clinicians to predict the optimal starting dosage and the need for a personalized adjustment of the dose, as well as to identify patients at a high risk of rejection, drug-related adverse effects, or poor outcomes. In the past decade, new pharmacokinetic strategies have been developed to improve personalized tacrolimus treatment. Several studies have shown that patients with tacrolimus doses C(0)/D < 1 ng/mL/mg may demonstrate a greater incidence of drug-related adverse events and infections. In addition, C(0) tacrolimus intrapatient variability (IPV) has been identified as a potential biomarker to predict poor outcomes related to drug over- and under-exposure. With regard to tacrolimus pharmacodynamics, inconsistent genotype-phenotype relationships have been identified. The aim of this review is to provide a concise summary of currently available data regarding the influence of pharmacogenetics on the clinical outcome of patients with high intrapatient variability and/or a fast metabolizer phenotype. Moreover, the role of membrane transporters in the interindividual variability of responses to tacrolimus is critically discussed from a transporter scientist’s perspective. Indeed, the relationship between transporter polymorphisms and intracellular tacrolimus concentrations will help to elucidate the interplay between the biological mechanisms underlying genetic variations impacting drug concentrations and clinical effects.
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spelling pubmed-95035582022-09-24 Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics Brunet, Mercè Pastor-Anglada, Marçal Pharmaceutics Review The influence of pharmacogenetics in tacrolimus pharmacokinetics and pharmacodynamics needs further investigation, considering its potential in assisting clinicians to predict the optimal starting dosage and the need for a personalized adjustment of the dose, as well as to identify patients at a high risk of rejection, drug-related adverse effects, or poor outcomes. In the past decade, new pharmacokinetic strategies have been developed to improve personalized tacrolimus treatment. Several studies have shown that patients with tacrolimus doses C(0)/D < 1 ng/mL/mg may demonstrate a greater incidence of drug-related adverse events and infections. In addition, C(0) tacrolimus intrapatient variability (IPV) has been identified as a potential biomarker to predict poor outcomes related to drug over- and under-exposure. With regard to tacrolimus pharmacodynamics, inconsistent genotype-phenotype relationships have been identified. The aim of this review is to provide a concise summary of currently available data regarding the influence of pharmacogenetics on the clinical outcome of patients with high intrapatient variability and/or a fast metabolizer phenotype. Moreover, the role of membrane transporters in the interindividual variability of responses to tacrolimus is critically discussed from a transporter scientist’s perspective. Indeed, the relationship between transporter polymorphisms and intracellular tacrolimus concentrations will help to elucidate the interplay between the biological mechanisms underlying genetic variations impacting drug concentrations and clinical effects. MDPI 2022-08-23 /pmc/articles/PMC9503558/ /pubmed/36145503 http://dx.doi.org/10.3390/pharmaceutics14091755 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 Review
Brunet, Mercè
Pastor-Anglada, Marçal
Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics
title Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics
title_full Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics
title_fullStr Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics
title_full_unstemmed Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics
title_short Insights into the Pharmacogenetics of Tacrolimus Pharmacokinetics and Pharmacodynamics
title_sort insights into the pharmacogenetics of tacrolimus pharmacokinetics and pharmacodynamics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503558/
https://www.ncbi.nlm.nih.gov/pubmed/36145503
http://dx.doi.org/10.3390/pharmaceutics14091755
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