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Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients

Rifampin (RF) is metabolized in the liver into an active metabolite 25-desacetylrifampin and excreted almost equally via biliary and renal routes. Various influx and efflux transporters influence RF disposition during hepatic uptake and biliary excretion. Evidence has also shown that Vitamin D defic...

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Autores principales: Thomas, Levin, Sekhar Miraj, Sonal, Surulivelrajan, Mallayasamy, Varma, Muralidhar, Sanju, Chidananda S. V., Rao, Mahadev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344705/
https://www.ncbi.nlm.nih.gov/pubmed/32521634
http://dx.doi.org/10.3390/antibiotics9060307
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author Thomas, Levin
Sekhar Miraj, Sonal
Surulivelrajan, Mallayasamy
Varma, Muralidhar
Sanju, Chidananda S. V.
Rao, Mahadev
author_facet Thomas, Levin
Sekhar Miraj, Sonal
Surulivelrajan, Mallayasamy
Varma, Muralidhar
Sanju, Chidananda S. V.
Rao, Mahadev
author_sort Thomas, Levin
collection PubMed
description Rifampin (RF) is metabolized in the liver into an active metabolite 25-desacetylrifampin and excreted almost equally via biliary and renal routes. Various influx and efflux transporters influence RF disposition during hepatic uptake and biliary excretion. Evidence has also shown that Vitamin D deficiency (VDD) and Vitamin D receptor (VDR) polymorphisms are associated with tuberculosis (TB). Hence, genetic polymorphisms of metabolizing enzymes, drug transporters and/or their transcriptional regulators and VDR and its pathway regulators may affect the pharmacokinetics of RF. In this narrative review, we aim to identify literature that has explored the influence of single nucleotide polymorphisms (SNPs) of genes encoding drug transporters and their transcriptional regulators (SLCO1B1, ABCB1, PXR and CAR), metabolizing enzymes (CES1, CES2 and AADAC) and VDR and its pathway regulators (VDR, CYP27B1 and CYP24A1) on plasma RF concentrations in TB patients on antitubercular therapy. Available reports to date have shown that there is a lack of any association of ABCB1, PXR, CAR, CES1 and AADAC genetic variants with plasma concentrations of RF. Further evidence is required from a more comprehensive exploration of the association of SLCO1B1, CES2 and Vitamin D pathway gene variants with RF pharmacokinetics in distinct ethnic groups and a larger population to reach conclusive information.
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spelling pubmed-73447052020-07-09 Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients Thomas, Levin Sekhar Miraj, Sonal Surulivelrajan, Mallayasamy Varma, Muralidhar Sanju, Chidananda S. V. Rao, Mahadev Antibiotics (Basel) Review Rifampin (RF) is metabolized in the liver into an active metabolite 25-desacetylrifampin and excreted almost equally via biliary and renal routes. Various influx and efflux transporters influence RF disposition during hepatic uptake and biliary excretion. Evidence has also shown that Vitamin D deficiency (VDD) and Vitamin D receptor (VDR) polymorphisms are associated with tuberculosis (TB). Hence, genetic polymorphisms of metabolizing enzymes, drug transporters and/or their transcriptional regulators and VDR and its pathway regulators may affect the pharmacokinetics of RF. In this narrative review, we aim to identify literature that has explored the influence of single nucleotide polymorphisms (SNPs) of genes encoding drug transporters and their transcriptional regulators (SLCO1B1, ABCB1, PXR and CAR), metabolizing enzymes (CES1, CES2 and AADAC) and VDR and its pathway regulators (VDR, CYP27B1 and CYP24A1) on plasma RF concentrations in TB patients on antitubercular therapy. Available reports to date have shown that there is a lack of any association of ABCB1, PXR, CAR, CES1 and AADAC genetic variants with plasma concentrations of RF. Further evidence is required from a more comprehensive exploration of the association of SLCO1B1, CES2 and Vitamin D pathway gene variants with RF pharmacokinetics in distinct ethnic groups and a larger population to reach conclusive information. MDPI 2020-06-08 /pmc/articles/PMC7344705/ /pubmed/32521634 http://dx.doi.org/10.3390/antibiotics9060307 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Thomas, Levin
Sekhar Miraj, Sonal
Surulivelrajan, Mallayasamy
Varma, Muralidhar
Sanju, Chidananda S. V.
Rao, Mahadev
Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients
title Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients
title_full Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients
title_fullStr Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients
title_full_unstemmed Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients
title_short Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients
title_sort influence of single nucleotide polymorphisms on rifampin pharmacokinetics in tuberculosis patients
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344705/
https://www.ncbi.nlm.nih.gov/pubmed/32521634
http://dx.doi.org/10.3390/antibiotics9060307
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