{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:33:10Z","timestamp":1793295190399,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,11,5]],"date-time":"2018-11-05T00:00:00Z","timestamp":1541376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23 AI097197"],"award-info":[{"award-number":["K23 AI097197"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI 115594"],"award-info":[{"award-number":["U01 AI 115594"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dosing recommendations for treating childhood tuberculosis (TB) were revised by the World Health Organization, yet so far, pharmacokinetic studies that have evaluated these changes are relatively limited. We evaluated plasma drug concentrations of rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) among children undergoing TB treatment in Tanzania when these dosing recommendations were being implemented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>At the end of intensive-phase TB therapy, blood was obtained 2 hours after witnessed medication administration to estimate the peak drug concentration (C2h), measured using high-performance liquid chromatography or liquid chromatography\u2013tandem mass spectrometry methods. Differences in median drug concentrations were compared on the basis of the weight-based dosing strategy using the Mann\u2013Whitney U test. Risk factors for low drug concentrations were analyzed using multivariate regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We enrolled 51 human immunodeficiency virus\u2013negative children (median age, 5.3 years [range, 0.75\u201314 years]). The median C2hs were below the target range for each TB drug studied. Compared with children who received the \u201cold\u201d dosages, those who received the \u201crevised\u201d WHO dosages had a higher median C2h for RIF (P = .049) and PZA (P = .015) but not for INH (P = .624) or EMB (P = .143); however, these revised dosages did not result in the target range for RIF, INH, and EMB being achieved. A low starting dose was associated with a low C2h for RIF (P = .005) and PZA (P = .005). Malnutrition was associated with a low C2h for RIF (P = .001) and INH (P = .001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Among this cohort of human immunodeficiency virus\u2013negative Tanzanian children, use of the revised dosing strategy for treating childhood TB did not result in the target drug concentration for RIF, INH, or EMB being reached.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jpids\/piy106","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T21:43:23Z","timestamp":1539812603000},"page":"14-20","source":"Crossref","is-referenced-by-count":25,"title":["Pharmacokinetics of First-Line Drugs Among Children With Tuberculosis in Rural Tanzania"],"prefix":"10.1093","volume":"9","author":[{"given":"Museveni","family":"Justine","sequence":"first","affiliation":[{"name":"Center for Global Health Research, Haydom Lutheran Hospital, Haydom, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Yeconia","sequence":"first","affiliation":[{"name":"Center for Global Health Research, Haydom Lutheran Hospital, Haydom, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingi","family":"Nicodemu","sequence":"first","affiliation":[{"name":"Center for Global Health Research, Haydom Lutheran Hospital, Haydom, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domitila","family":"Augustino","sequence":"first","affiliation":[{"name":"Center for Global Health Research, Haydom Lutheran Hospital, Haydom, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Gratz","sequence":"first","affiliation":[{"name":"Center for Global Health Research, Haydom Lutheran Hospital, Haydom, Tanzania"},{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-3982","authenticated-orcid":false,"given":"Estomih","family":"Mduma","sequence":"first","affiliation":[{"name":"Center for Global Health Research, Haydom Lutheran Hospital, Haydom, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott K","family":"Heysell","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sokoine","family":"Kivuyo","sequence":"first","affiliation":[{"name":"National Institute of Medical Research Muhimbili, Dar es Salaam, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayoki","family":"Mfinanga","sequence":"first","affiliation":[{"name":"National Institute of Medical Research Muhimbili, Dar es Salaam, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A","family":"Peloquin","sequence":"first","affiliation":[{"name":"Infectious Disease Pharmacokinetic Laboratory, University of Florida, Gainesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Zagurski","sequence":"first","affiliation":[{"name":"Infectious Disease Pharmacokinetic Laboratory, University of Florida, Gainesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gibson S","family":"Kibiki","sequence":"first","affiliation":[{"name":"East African Health Research Commission, East African Community, Arusha, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blandina","family":"Mmbaga","sequence":"first","affiliation":[{"name":"Kilimanjaro Clinical Research Institute, Kilimanjaro Christian Medical College, Moshi, Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric R","family":"Houpt","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania A","family":"Thomas","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Health, University of Virginia, Charlottesville"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,5]]},"reference":[{"key":"2020062603134446400_CIT0001","first-page":"262","volume-title":"Global tuberculosis report 2017. 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