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

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dc.contributor.author이민구-
dc.contributor.author윤지훈-
dc.date.accessioned2021-12-28T17:25:50Z-
dc.date.available2021-12-28T17:25:50Z-
dc.date.issued2021-04-
dc.identifier.issn1744-6872-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/187096-
dc.description.abstractIsoniazid 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.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherLippincott Williams & Wilkins-
dc.relation.isPartOfPHARMACOGENETICS AND GENOMICS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAdult-
dc.subject.MESHAntitubercular Agents / administration & dosage-
dc.subject.MESHAntitubercular Agents / adverse effects-
dc.subject.MESHArylamine N-Acetyltransferase / genetics*-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHFemale-
dc.subject.MESHGenotype-
dc.subject.MESHHealthy Volunteers-
dc.subject.MESHHumans-
dc.subject.MESHIsoniazid / administration & dosage*-
dc.subject.MESHIsoniazid / adverse effects-
dc.subject.MESHLatent Tuberculosis / drug therapy*-
dc.subject.MESHLatent Tuberculosis / genetics*-
dc.subject.MESHLatent Tuberculosis / microbiology-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHPilot Projects-
dc.titleA pilot study to investigate the utility of NAT2 genotype-guided isoniazid monotherapy regimens in NAT2 slow acetylators-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pharmacology (약리학교실)-
dc.contributor.googleauthorHyounggyoon Yoo-
dc.contributor.googleauthorSang Chun Ji-
dc.contributor.googleauthorJoo-Youn Cho-
dc.contributor.googleauthorSang-Heon Kim-
dc.contributor.googleauthorJihoon G Yoon-
dc.contributor.googleauthorMin Goo Lee-
dc.contributor.googleauthorKyung-Sang Yu-
dc.contributor.googleauthorIn-Jin Jang-
dc.contributor.googleauthorJaeseong Oh-
dc.identifier.doi10.1097/FPC.0000000000000423-
dc.contributor.localIdA02781-
dc.relation.journalcodeJ02506-
dc.identifier.eissn1744-6880-
dc.identifier.pmid33165168-
dc.identifier.urlhttps://journals.lww.com/jpharmacogenetics/Fulltext/2021/04000/A_pilot_study_to_investigate_the_utility_of_NAT2.3.aspx-
dc.contributor.alternativeNameLee, Min Goo-
dc.contributor.affiliatedAuthor이민구-
dc.citation.volume31-
dc.citation.number3-
dc.citation.startPage68-
dc.citation.endPage73-
dc.identifier.bibliographicCitationPHARMACOGENETICS AND GENOMICS, Vol.31(3) : 68-73, 2021-04-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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