{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:34:09Z","timestamp":1790102049374,"version":"4.0.1"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"This publication was produced by PanACEA, which is part of the European and Developing Countries Clinical Trials Partnership 2 (EDCTP2) programme, supported by the European Union","award":["TRIA2015-1102-PanACEA"],"award-info":[{"award-number":["TRIA2015-1102-PanACEA"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,10,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg\/kg daily, RIF40) and standard-dose rifampicin (10 mg\/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1\u201315), followed by RIF40 (days 16\u201330). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%\u2013115%); tolbutamide, 80% (74%\u201386%); omeprazole, 55% (47%\u201365%); dextromethorphan, 77% (68%\u201386%); midazolam, 62% (49%\u201378%), and 117% (105%\u2013130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT04525235\" xlink:type=\"simple\">NCT04525235<\/jats:ext-link>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00683-23","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T14:39:19Z","timestamp":1695911959000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis"],"prefix":"10.1128","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6912-4163","authenticated-orcid":false,"given":"Ralf","family":"Stemkens","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique de","family":"Jager","sequence":"additional","affiliation":[{"name":"TASK , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Dawson","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Department of Medicine, University of Cape Town and University of Cape Town Lung Institute , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas H.","family":"Diacon","sequence":"additional","affiliation":[{"name":"TASK , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Narunsky","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Department of Medicine, University of Cape Town and University of Cape Town Lung Institute , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherman D.","family":"Padayachee","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Department of Medicine, University of Cape Town and University of Cape Town Lung Institute , Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Boeree","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stijn W.","family":"van Beek","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Colbers","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute for Medical Innovation, Radboud University Medical Center , Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke J. 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