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Isoniazid, rifampin, and pyrazinamide concentration\u2013time profiles and treatment outcome were obtained from 161 Indian children with drug\u2010sensitive tuberculosis undergoing thrice\u2010weekly dosing as per previous Indian pediatric guidelines. The exposure\u2013response relationships were established using a population pharmacokinetic\u2010pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4\u20137\u2009kg) and\/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (P<jats:sub>unfavorable<\/jats:sub>). Model\u2010based simulation of optimized (P<jats:sub>unfavorable<\/jats:sub> \u2264 5%) rifampin once\u2010daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose\u2010exposure\u2013response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines.<\/jats:p>","DOI":"10.1002\/cpt.987","type":"journal-article","created":{"date-parts":[[2017,12,16]],"date-time":"2017-12-16T22:52:14Z","timestamp":1513464734000},"page":"733-741","source":"Crossref","is-referenced-by-count":30,"title":["Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV\u2010Coinfected Children in India: Recommendations for Dose Modifications"],"prefix":"10.1111","volume":"104","author":[{"given":"Benjamin","family":"Guiastrennec","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geetha","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"National Institute for Research in Tuberculosis, Indian Council of Medical Research Chetpet Chennai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mats O.","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.K. 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