Short CommunicationA pilot study to investigate the utility of NAT2 genotype-guided isoniazid monotherapy regimens in NAT2 slow acetylatorsYoo, Hyounggyoona,,*; Chun Ji, Sanga,,*; Cho, Joo-Youna; Kim, Sang-Heonb; Yoon, Jihoon G.c; Goo Lee, Minc; Yu, Kyung-Sanga; Jang, In-Jina; Oh, Jaeseonga Author Information aDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital bDepartment of Internal Medicine, Hanyang University College of Medicine cDepartment of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea *Dr. Hyounggyoon Yoo and Dr Sang Chun Ji contributed equally to the writing of this article. Received 11 May 2020 Accepted 16 August 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.pharmacogeneticsandgenomics.com. Correspondence to Jaeseong Oh, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea, Tel: +82 2 2072 4082; fax: +82 2 742 9252; e-mail: [email protected] Pharmacogenetics and Genomics: April 2021 - Volume 31 - Issue 3 - p 68-73 doi: 10.1097/FPC.0000000000000423 Buy SDC Metrics 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.