Influence of single nucleotide polymorphisms on rifampin pharmacokinetics in tuberculosis patients

Thomas, Levin and Sekhar, Sonal M and Surulivelrajan, Mallayasamy and Varma, Muralidhar and Rao, Mahadev (2020) Influence of single nucleotide polymorphisms on rifampin pharmacokinetics in tuberculosis patients. Antibiotics, 9 (6). pp. 1-15. ISSN 2079-6382

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Abstract

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 e�ux 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 a�ect 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.

Item Type: Article
Uncontrolled Keywords: Tuberculosis; rifampin; single nucleotide polymorphisms; SLCO1B1; pharmacokinetics.
Subjects: Medicine > KMC Manipal > Medicine
Pharmacy > MCOPS Manipal > Pharmacy Practice
Depositing User: KMC Library
Date Deposited: 22 Sep 2020 05:31
Last Modified: 22 Sep 2020 05:31
URI: http://eprints.manipal.edu/id/eprint/155661

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