A pilot study to investigate the utility of NAT2 genotype-guided isoniazid monotherapy regimens in NAT2 slow acetylators
- Authors
- Yoo, Hyounggyoon; Ji, Sang Chun; Cho, Joo-Youn; Kim, Sang-Heon; Yoon, Jihoon G.; Lee, Min Goo; Yu, Kyung-Sang; Jang, In-Jin; Oh, Jaeseong
- Issue Date
- Apr-2021
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- adverse drug reactions; isoniazid monotherapy; NAT2 genotype; pharmacogenomics
- Citation
- PHARMACOGENETICS AND GENOMICS, v.31, no.3, pp.68 - 73
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHARMACOGENETICS AND GENOMICS
- Volume
- 31
- Number
- 3
- Start Page
- 68
- End Page
- 73
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/1256
- DOI
- 10.1097/FPC.0000000000000423
- ISSN
- 1744-6872
- Abstract
- Isoniazid is a therapeutic agent for the treatment of latent tuberculosis infection. Genetic variants in the N-acetyltransferase 2 (NAT2) are associated with the safety and pharmacokinetics of isoniazid. The study aimed to evaluate the safety and pharmacokinetics of a NAT2 genotype-guided regimen of isoniazid monotherapy. A randomized, open-label, parallel-group and multiple-dosing study was performed in healthy subjects. The subjects received isoniazid for 29 days. The NAT2 slow acetylators (NAT2*5/*5, -*5/*6, -*5/*7, -*6/*6, -*6/*7, -*7/*7) randomly received standard dose (300 mg, standard-treatment group) or reduced dose (200 mg, PGx-treatment group) of isoniazid. Also, all the NAT2 rapid acetylators (NAT2*4/*4) received isoniazid 300 mg (reference group). The safety and pharmacokinetics were evaluated during the study. The PGx-treatment group showed a more stable serum liver enzyme profile and a lower incidence of adverse drug reactions (ADRs) than the standard-treatment group. The emergence rates of ADRs were 12.5, 60 and 33.3% in the reference, standard-treatment and PGx-treatment groups, respectively. The PGx-treatment group showed higher plasma isoniazid concentrations than the reference group, although the PGx-treatment group received a reduced dose of isoniazid. Our results showed that a NAT2 genotype-guided regimen may reduce ADRs during isoniazid monotherapy without concern over insufficient drug exposure.
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