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Open AccessReview

Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients

1
Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
2
Department of Infectious Diseases, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
3
District Tuberculosis Control Office, Ajjarakad, Udupi, Karnataka 576001, India
*
Author to whom correspondence should be addressed.
Antibiotics 2020, 9(6), 307; https://doi.org/10.3390/antibiotics9060307
Received: 6 May 2020 / Revised: 29 May 2020 / Accepted: 3 June 2020 / Published: 8 June 2020
(This article belongs to the Special Issue Synthesis and Pharmacokinetics of Antibiotics)
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. View Full-Text
Keywords: tuberculosis; rifampin; single nucleotide polymorphisms; SLCO1B1; pharmacokinetics tuberculosis; rifampin; single nucleotide polymorphisms; SLCO1B1; pharmacokinetics
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MDPI and ACS Style

Thomas, L.; Sekhar Miraj, S.; Surulivelrajan, M.; Varma, M.; Sanju, C.S.V.; Rao, M. Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients. Antibiotics 2020, 9, 307. https://doi.org/10.3390/antibiotics9060307

AMA Style

Thomas L, Sekhar Miraj S, Surulivelrajan M, Varma M, Sanju CSV, Rao M. Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients. Antibiotics. 2020; 9(6):307. https://doi.org/10.3390/antibiotics9060307

Chicago/Turabian Style

Thomas, Levin; Sekhar Miraj, Sonal; Surulivelrajan, Mallayasamy; Varma, Muralidhar; Sanju, Chidananda S.V.; Rao, Mahadev. 2020. "Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients" Antibiotics 9, no. 6: 307. https://doi.org/10.3390/antibiotics9060307

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