{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:41:57Z","timestamp":1775886117673,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005375","name":"Latvian Council of Science","doi-asserted-by":"publisher","award":["lzp2020\/1-0050"],"award-info":[{"award-number":["lzp2020\/1-0050"]}],"id":[{"id":"10.13039\/501100005375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Genetic 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\u201312 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 AUC0\u20136 h in comparison to those with GG genotype, while the difference in RIF plasma Cmax 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics16030388","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T12:14:40Z","timestamp":1710245680000},"page":"388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploring Variability in Rifampicin Plasma Exposure and Development of Anti-Tuberculosis Drug-Induced Liver Injury among Patients with Pulmonary Tuberculosis from the Pharmacogenetic Perspective"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-2011","authenticated-orcid":false,"given":"Agnija","family":"Kivrane","sequence":"first","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Ratsupites Street 1, k-1, LV1067 Riga, Latvia"},{"name":"Pharmacogenetic and Precision Medicine Laboratory, Pharmaceutical Education and Research Centre, Riga Stradins University, Konsula Street 21, LV1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktorija","family":"Ulanova","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Ratsupites Street 1, k-1, LV1067 Riga, Latvia"},{"name":"Pharmacogenetic and Precision Medicine Laboratory, Pharmaceutical Education and Research Centre, Riga Stradins University, Konsula Street 21, LV1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solveiga","family":"Grinberga","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Group, Latvian Institute of Organic Synthesis, Aizkraukles Street 21, LV1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduards","family":"Sevostjanovs","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Group, Latvian Institute of Organic Synthesis, Aizkraukles Street 21, LV1006 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anda","family":"Viksna","sequence":"additional","affiliation":[{"name":"Riga East University Hospital, Centre of Tuberculosis and Lung Diseases, Stopini Region, LV2118 Upeslejas, Latvia"},{"name":"Department of Infectiology, Riga Stradins University, Dzirciema Street 16, LV1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iveta","family":"Ozere","sequence":"additional","affiliation":[{"name":"Riga East University Hospital, Centre of Tuberculosis and Lung Diseases, Stopini Region, LV2118 Upeslejas, Latvia"},{"name":"Department of Infectiology, Riga Stradins University, Dzirciema Street 16, LV1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ineta","family":"Bogdanova","sequence":"additional","affiliation":[{"name":"Riga East University Hospital, Centre of Tuberculosis and Lung Diseases, Stopini Region, LV2118 Upeslejas, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9120-5869","authenticated-orcid":false,"given":"Maksims","family":"Zolovs","sequence":"additional","affiliation":[{"name":"Statistics Unit, Riga Stradins University, Dzirciema Street 16, LV1007 Riga, Latvia"},{"name":"Institute of Life Sciences and Technology, Daugavpils University, Parades Street 1a, LV5401 Daugavpils, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renate","family":"Ranka","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Ratsupites Street 1, k-1, LV1067 Riga, Latvia"},{"name":"Pharmacogenetic and Precision Medicine Laboratory, Pharmaceutical Education and Research Centre, Riga Stradins University, Konsula Street 21, LV1007 Riga, Latvia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"ref_1","unstructured":"(2022). 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