{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:32:20Z","timestamp":1790872340643,"version":"4.1.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The currently recommended doses of rifampin are believed to be at the lower end of the dose-response curve. Rifampin induces its own metabolism, although the effect of dose on the extent of autoinduction is not known. This study aimed to investigate rifampin autoinduction using a semimechanistic pharmacokinetic-enzyme turnover model. Four different structural basic models were explored to assess whether different scaling methods affected the final covariate selection procedure. Covariates were selected by using a linearized approach. The final model included the allometric scaling of oral clearance and apparent volume of distribution. Although HIV infection was associated with a 30% increase in the apparent volume of distribution, simulations demonstrated that the effect of HIV on rifampin exposure was slight. Model-based simulations showed close-to-maximum induction achieved after 450-mg daily dosing, since negligible increases in oral clearance were observed following the 600-mg\/day regimen. Thus, dosing above 600 mg\/day is unlikely to result in higher magnitudes of autoinduction. In a typical 55-kg male without HIV infection, the oral clearance, which was 7.76 liters \u00b7 h\n            <jats:sup>\u22121<\/jats:sup>\n            at the first dose, increased 1.82- and 1.85-fold at steady state after daily dosing with 450 and 600 mg, respectively. Corresponding reductions of 41 and 42%, respectively, in the area under the concentration-versus-time curve from 0 to 24 h were estimated. The turnover of the inducible process was estimated to have a half-life of approximately 8 days in a typical patient. Assuming 5 half-lives to steady state, this corresponds to a duration of approximately 40 days to reach the induced state for rifampin autoinduction.\n          <\/jats:p>","DOI":"10.1128\/aac.05792-11","type":"journal-article","created":{"date-parts":[[2012,1,18]],"date-time":"2012-01-18T05:13:08Z","timestamp":1326863588000},"page":"2091-2098","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":82,"title":["A Semimechanistic Pharmacokinetic-Enzyme Turnover Model for Rifampin Autoinduction in Adult Tuberculosis Patients"],"prefix":"10.1128","volume":"56","author":[{"given":"Wynand","family":"Smythe","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akash","family":"Khandelwal","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Merle","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Tropical Epidemiological Group, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Rustomjee","sequence":"additional","affiliation":[{"name":"Unit for Clinical and Biomedical TB Research, Medical Research Council, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Gninafon","sequence":"additional","affiliation":[{"name":"Programme National de Lutte contre la Tuberculose, BP 817, Cotonou, B\u00e9nin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mame","family":"Bocar Lo","sequence":"additional","affiliation":[{"name":"Programme National de Lutte contre la Tuberculose, BP 5899, Dakar-Fann, S\u00e9n\u00e9gal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oumou Bah","family":"Sow","sequence":"additional","affiliation":[{"name":"Service Pneumo-phtisiologie, CHU Ignace Deen, BP 634, Conakry, Guinea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero L.","family":"Olliaro","sequence":"additional","affiliation":[{"name":"UNICEF\/UNDP\/World Bank\/WHO Special Programme on Research and Training in Tropical Diseases (TDR), World Health Organization, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lienhardt","sequence":"additional","affiliation":[{"name":"Institut de Recherche pour le D\u00e9veloppement, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Horton","sequence":"additional","affiliation":[{"name":"Tropical Projects, Hitchin, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"McIlleron","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika S. 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