{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T19:05:20Z","timestamp":1774897520437,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare","award":["MOHW106-CDC-C-11400104; MOHW107-CDC-C-114-000105"],"award-info":[{"award-number":["MOHW106-CDC-C-11400104; MOHW107-CDC-C-114-000105"]}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST106-2314-B-002-055; MOST107-2314-B-002-191; MOST107-2314-B-037-106-MY3"],"award-info":[{"award-number":["MOST106-2314-B-002-055; MOST107-2314-B-002-191; MOST107-2314-B-037-106-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Weekly rifapentine and isoniazid therapy (known as 3HP) for latent tuberculosis infection (LTBI) is increasingly used, but systemic drug reactions (SDR) remain a major concern. Methods: We prospectively recruited two LTBI cohorts who received the 3HP regimen. In the single-nucleotide polymorphism (SNP) cohort, we collected clinical information of SDRs and examined the NAT2, CYP2E1, and AADAC SNPs. In the pharmacokinetic (PK) cohort, we measured plasma drug and metabolite levels at 6 and 24 h after 3HP administration. The generalised estimating equation model was used to identify the factors associated with SDRs. Candidate SNPs predicting SDRs were validated in the PK cohort. A total of 177 participants were recruited into the SNP cohort and 129 into the PK cohort, with 14 (8%) and 13 (10%) in these two cohorts developing SDRs, respectively. In the SNP cohort, NAT2 rs1041983 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 7.00 [2.03\u201324.1]) and CYP2E1 rs2070673 (AA vs. TT+TA, OR [95% CI]: 3.50 [1.02\u201312.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 h after 3HP administration (OR [95% CI]: 1.61 [1.15\u20132.25]) was associated with SDRs. Additionally, the association between the NAT2 SNP and SDRs was validated in the PK cohort (rs1041983 TT vs. CC+CT, OR [95% CI]: 4.43 [1.30\u201315.1]). Conclusions: Isoniazid played a role in the development of 3HP-related SDRs. This could provide insight for further design of a more optimal regimen for latent TB infection.<\/jats:p>","DOI":"10.3390\/jcm8060812","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T03:56:31Z","timestamp":1559879791000},"page":"812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7220-4833","authenticated-orcid":false,"given":"Meng-Rui","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital, Hsinchu Branch, Hsinchu 30059, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Ling","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Hsuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan"},{"name":"School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Departments of Respiratory Therapy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So-Yi","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, National Taiwan University Medical College, Taipei 10051, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9613-4788","authenticated-orcid":false,"given":"Bo-Shiun","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, National Taiwan University Medical College, Taipei 10051, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Hua","family":"Kuo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po-Liang","family":"Lu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-366X","authenticated-orcid":false,"given":"Jann-Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inn-Wen","family":"Chong","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Departments of Respiratory Therapy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018). 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