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A pilot study to investigate the utility of NAT2 genotype-guided isoniazid monotherapy regimens in NAT2 slow acetylators

Authors
 Hyounggyoon Yoo  ;  Sang Chun Ji  ;  Joo-Youn Cho  ;  Sang-Heon Kim  ;  Jihoon G Yoon  ;  Min Goo Lee  ;  Kyung-Sang Yu  ;  In-Jin Jang  ;  Jaeseong Oh 
Citation
 PHARMACOGENETICS AND GENOMICS, Vol.31(3) : 68-73, 2021-04 
Journal Title
PHARMACOGENETICS AND GENOMICS
ISSN
 1744-6872 
Issue Date
2021-04
MeSH
Adult ; Antitubercular Agents / administration & dosage ; Antitubercular Agents / adverse effects ; Arylamine N-Acetyltransferase / genetics* ; Dose-Response Relationship, Drug ; Female ; Genotype ; Healthy Volunteers ; Humans ; Isoniazid / administration & dosage* ; Isoniazid / adverse effects ; Latent Tuberculosis / drug therapy* ; Latent Tuberculosis / genetics* ; Latent Tuberculosis / microbiology ; Male ; Middle Aged ; Pilot Projects
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.
Full Text
https://journals.lww.com/jpharmacogenetics/Fulltext/2021/04000/A_pilot_study_to_investigate_the_utility_of_NAT2.3.aspx
DOI
10.1097/FPC.0000000000000423
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Jihoon G.(윤지훈) ORCID logo https://orcid.org/0000-0002-4401-7803
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187096
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