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Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI

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 (S...

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Autores principales: Lee, Meng-Rui, Huang, Hung-Ling, Lin, Shu-Wen, Cheng, Meng-Hsuan, Lin, Ya-Ting, Chang, So-Yi, Yan, Bo-Shiun, Kuo, Ching-Hua, Lu, Po-Liang, Wang, Jann-Yuan, Chong, Inn-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616849/
https://www.ncbi.nlm.nih.gov/pubmed/31174321
http://dx.doi.org/10.3390/jcm8060812
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author Lee, Meng-Rui
Huang, Hung-Ling
Lin, Shu-Wen
Cheng, Meng-Hsuan
Lin, Ya-Ting
Chang, So-Yi
Yan, Bo-Shiun
Kuo, Ching-Hua
Lu, Po-Liang
Wang, Jann-Yuan
Chong, Inn-Wen
author_facet Lee, Meng-Rui
Huang, Hung-Ling
Lin, Shu-Wen
Cheng, Meng-Hsuan
Lin, Ya-Ting
Chang, So-Yi
Yan, Bo-Shiun
Kuo, Ching-Hua
Lu, Po-Liang
Wang, Jann-Yuan
Chong, Inn-Wen
author_sort Lee, Meng-Rui
collection PubMed
description 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 [2.03–24.1]) and CYP2E1 rs2070673 (AA vs. TT+TA, OR [95% CI]: 3.50 [1.02–12.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 h after 3HP administration (OR [95% CI]: 1.61 [1.15–2.25]) 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 [1.30–15.1]). 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.
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spelling pubmed-66168492019-07-18 Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI Lee, Meng-Rui Huang, Hung-Ling Lin, Shu-Wen Cheng, Meng-Hsuan Lin, Ya-Ting Chang, So-Yi Yan, Bo-Shiun Kuo, Ching-Hua Lu, Po-Liang Wang, Jann-Yuan Chong, Inn-Wen J Clin Med Article 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 [2.03–24.1]) and CYP2E1 rs2070673 (AA vs. TT+TA, OR [95% CI]: 3.50 [1.02–12.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 h after 3HP administration (OR [95% CI]: 1.61 [1.15–2.25]) 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 [1.30–15.1]). 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. MDPI 2019-06-06 /pmc/articles/PMC6616849/ /pubmed/31174321 http://dx.doi.org/10.3390/jcm8060812 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Meng-Rui
Huang, Hung-Ling
Lin, Shu-Wen
Cheng, Meng-Hsuan
Lin, Ya-Ting
Chang, So-Yi
Yan, Bo-Shiun
Kuo, Ching-Hua
Lu, Po-Liang
Wang, Jann-Yuan
Chong, Inn-Wen
Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI
title Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI
title_full Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI
title_fullStr Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI
title_full_unstemmed Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI
title_short Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI
title_sort isoniazid concentration and nat2 genotype predict risk of systemic drug reactions during 3hp for ltbi
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616849/
https://www.ncbi.nlm.nih.gov/pubmed/31174321
http://dx.doi.org/10.3390/jcm8060812
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