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The purpose of this study is to determine the association of rifapentine or isoniazid concentration and ADRs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This prospective, multicentre, observational study enrolled LTBI contacts receiving 3HP treatment between January 2017 and August 2020. The concentrations of rifapentine, isoniazid and their metabolites (25\u2010desacetyl\u2010rifapentine and acetyl\u2010isoniazid) in plasma samples collected monthly after 3HP treatment were determined. A PPK model was constructed to predict the maximum concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) and area under the concentration\u2013time curve from 0 to 24\u2009h (AUC). Their association with ADRs was evaluated by applying three multivariate logistic regression models with adjustment for various covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 415 LTBI cases were ultimately enrolled; 355 (85.5%) completed the 3HP treatment. Among them, 47 (11.3%) experienced systemic drug reactions and 291 (70.0%) experienced one or more flu\u2010like symptom. The plasma concentration\u2013time profiles of isoniazid, rifapentine and their metabolites were adequately described by the developed models. A higher <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of isoniazid was significantly correlated with a higher risk of any ADR (adjusted odds ratio and 95% confidence interval: 3.04 [1.07\u20138.65]) and any or at least two flu\u2010like symptoms (all severity grades) (2.76 [1.06\u20137.17]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Isoniazid may be responsible for ADRs, especially flu\u2010like symptoms, during 3HP treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15527","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T03:38:18Z","timestamp":1663126698000},"page":"714-726","source":"Crossref","is-referenced-by-count":9,"title":["Isoniazid level and flu\u2010like symptoms during rifapentine\u2010based tuberculosis preventive therapy: A population pharmacokinetic analysis"],"prefix":"10.1111","volume":"89","author":[{"given":"Ming\u2010Chia","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pharmacy New Taipei City Hospital  New Taipei City Taiwan"},{"name":"School of Pharmacy, College of Pharmacy Taipei Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuito","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacokinetics Graduate School of Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Muraki","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacokinetics Graduate School of Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"Kaohsiung Municipal Ta\u2010Tung Hospital, Kaohsiung Medical University Hospital  Kaohsiung 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