Exploring Variability in Rifampicin Plasma Exposure and Development of Anti-Tuberculosis Drug-Induced Liver Injury among Patients with Pulmonary Tuberculosis from the Pharmacogenetic Perspective

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dc.contributor.authorKivrane, Agnija
dc.contributor.authorUlanova, Viktorija
dc.contributor.authorGrinberga, Solveiga
dc.contributor.authorSevostjanovs, Eduards
dc.contributor.authorViksna, Anda
dc.contributor.authorOzere, Iveta
dc.contributor.authorBogdanova, Ineta
dc.contributor.authorZolovs, Maksims
dc.contributor.authorRanka, Renate
dc.contributor.institutionResearch Professor (Tenured Professor) Group at the Faculty of Pharmacy
dc.contributor.institutionDepartment of Infectology
dc.contributor.institutionStatistics Unit
dc.date.accessioned2024-04-04T09:00:02Z
dc.date.available2024-04-04T09:00:02Z
dc.date.issued2024-03-12
dc.descriptionPublisher Copyright: © 2024 by the authors.
dc.description.abstractGenetic polymorphisms can exert a considerable impact on drug pharmacokinetics (PK) and the development of adverse drug reactions (ADR). However, the effect of genetic polymorphisms on the anti-tuberculosis (anti-TB) drug, and particularly rifampicin (RIF), exposure or anti-TB drug-induced liver injury (DILI) remains uncertain. Here, we evaluated the relationship between single nucleotide polymorphisms (SNPs) detected in the RIF pharmacogenes ( AADAC, SLCO1B1, SLCO1B3, ABCB1, and NR1I2) and RIF PK parameters, as well as anti-TB treatment-associated DILI. In total, the study enrolled 46 patients with drug-susceptible pulmonary TB. The RIF plasma concentration was measured using the LC-MS/MS method in the blood samples collected pre-dose and 2 and 6 h post-dose, whilst the DILI status was established using the results from blood biochemical analysis performed before and 10-12 days after treatment onset. The genotyping was conducted using a targeted NGS approach. After adjustment for confounders, the patients carrying the rs3732357 GA/AA genotype of the NR1I2 gene were found to have significantly lower RIF plasma AUC 0-6 h in comparison to those with GG genotype, while the difference in RIF plasma C max was insignificant. None of the analyzed SNPs was related to DILI. Hence, we are the first to report NR1I2 intronic SNP rs3732357 as the genetic component of variability in RIF exposure. Regarding anti-TB treatment-associated DILI, the other preexisting factors promoting this ADR should be considered.en
dc.description.statusPeer reviewed
dc.format.extent1648727
dc.identifier.citationKivrane, A, Ulanova, V, Grinberga, S, Sevostjanovs, E, Viksna, A, Ozere, I, Bogdanova, I, Zolovs, M & Ranka, R 2024, 'Exploring Variability in Rifampicin Plasma Exposure and Development of Anti-Tuberculosis Drug-Induced Liver Injury among Patients with Pulmonary Tuberculosis from the Pharmacogenetic Perspective', Pharmaceutics, vol. 16, no. 3, 388. https://doi.org/10.3390/pharmaceutics16030388
dc.identifier.doi10.3390/pharmaceutics16030388
dc.identifier.issn1999-4923
dc.identifier.otherPubMedCentral: PMC10974048
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/15418
dc.identifier.urlhttps://www-webofscience-com.db.rsu.lv/wos/alldb/full-record/MEDLINE:38543282
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85188998129&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofPharmaceutics
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectSDG 3 - Good Health and Well-being
dc.titleExploring Variability in Rifampicin Plasma Exposure and Development of Anti-Tuberculosis Drug-Induced Liver Injury among Patients with Pulmonary Tuberculosis from the Pharmacogenetic Perspectiveen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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