https://scholars.lib.ntu.edu.tw/handle/123456789/614522
標題: | Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI | 作者: | MENG-RUI LEE Huang, Hung-Ling SHU-WEN LIN Cheng, Meng-Hsuan Lin, Ya-Ting Chang, So-Yi BO-SHIUN YAN CHING-HUA KUO Lu, Po-Liang JANN-YUAN WANG Chong, Inn-Wen |
關鍵字: | N-acetyltransferase 2; isoniazid; latent tuberculosis infection; rifapentine; systemic drug reaction | 公開日期: | 6-六月-2019 | 出版社: | MDPI | 卷: | 8 | 期: | 6 | 來源出版物: | Journal of clinical medicine | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/614522 | ISSN: | 2077-0383 | DOI: | 10.3390/jcm8060812 |
顯示於: | 醫學系 |
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