{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:08:19Z","timestamp":1793826499277,"version":"4.6.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T00:00:00Z","timestamp":1627862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004441","name":"Swedish International Development Cooperation Agency","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004441","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the effects of concomitant efavirenz-based ART and genetic polymorphism on the variability in rifampicin and 25-desacetylrifampicin pharmacokinetics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and methods<\/jats:title>\n                  <jats:p>Plasma concentrations of rifampicin and 25-desacetylrifampicin from 63 patients coinfected with TB and HIV were analysed by LC-MS\/MS followed by non-linear mixed-effects modelling. Patients were genotyped for SLCO1B1 (463 C&amp;gt;A, 388 A&amp;gt;G, 11187 G&amp;gt;A, rs4149015, 521 T&amp;gt;C and 1436 G&amp;gt;C) and SLCO1B3 (334 T&amp;gt;G).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>One-compartment disposition models described the observations adequately. The oral clearances of rifampicin and 25-desacetylrifampicin were 140% and 110% higher, respectively, in patients on concomitant efavirenz-based ART. Rifampicin bioavailability was also lower in patients on concomitant ART. Further, although not included in the final model, a lower relative bioavailability in carriers of WT SLCO1B3 334 T&amp;gt;G compared with carriers of mutations in the genotype was estimated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The results presented indicate both pre-systemic and systemic induction by efavirenz-based ART affecting rifampicin pharmacokinetics. The described drug\u2013drug interaction has a clinical impact on rifampicin exposure prior to steady state and may impact the early bactericidal activity in patients on efavirenz-based ART.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab258","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T19:11:41Z","timestamp":1625857901000},"page":"2950-2957","source":"Crossref","is-referenced-by-count":12,"title":["Effect of efavirenz-based ART on the pharmacokinetics of rifampicin and its primary metabolite in patients coinfected with TB and HIV"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5395-9819","authenticated-orcid":false,"given":"Jesper","family":"Sundell","sequence":"first","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"Bienvenu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Pharmacy, University of Rwanda, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"\u00c4bel\u00f6","sequence":"additional","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ashton","sequence":"additional","affiliation":[{"name":"Unit for Pharmacokinetics and Drug Metabolism, Department of Pharmacology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, 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