A proposal for an individualized pharmacogenetic-guided isoniazid dosage regimen for patients with tuberculosis
DC Field | Value | Language |
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dc.contributor.author | Jung, Jin Ah | - |
dc.contributor.author | Kim, Tae-Eun | - |
dc.contributor.author | Lee, Hyun | - |
dc.contributor.author | Jeong, Byeong-Ho | - |
dc.contributor.author | Park, Hye Yun | - |
dc.contributor.author | Jeon, Kyeongman | - |
dc.contributor.author | Kwon, O. Jung | - |
dc.contributor.author | Ko, Jae-Wook | - |
dc.contributor.author | Choi, Rihwa | - |
dc.contributor.author | Woo, Hye-In | - |
dc.date.accessioned | 2022-07-15T20:59:33Z | - |
dc.date.available | 2022-07-15T20:59:33Z | - |
dc.date.created | 2021-05-13 | - |
dc.date.issued | 2015-09 | - |
dc.identifier.issn | 11778881 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/156343 | - |
dc.description.abstract | Background/aim: Isoniazid (INH) is an essential component of first-line anti-tuberculosis (TB) treatment. However, treatment with INH is complicated by polymorphisms in the expression of the enzyme system primarily responsible for its elimination, N-acetyltransferase 2 (NAT2), and its associated hepatotoxicity. The objective of this study was to develop an individualized INH dosing regimen using a pharmacogenetic-driven model and to apply this regimen in a pilot study. Methods: A total of 206 patients with TB who received anti-TB treatment were included in this prospective study. The 2-hour post-dose concentrations of INH were obtained, and their NAT2 genotype was determined using polymerase chain reaction and sequencing. A multivariate regression analysis that included the variables of age, sex, body weight, and NAT2 genotype was performed to determine the best model for estimating the INH dose that achieves a concentration of 3.0-6.0 mg/L. This dosing algorithm was then used for newly enrolled 53 patients. Results: Serum concentrations of INH were significantly lower in the rapid-acetylators than in the slow-acetylators (2.55 mg/L vs 6.78 mg/L, median, P,0.001). A multivariate stepwise linear regression analysis revealed that NAT2 and body weight independently affected INH concentrations: INH concentration (mg/L) =13.821-0.1× (body weight, kg) −2.273× (number of high activity alleles of NAT2; 0, 1, 2). In 53 newly enrolled patients, the frequency at which they were within the therapeutic range of 3.0-6.0 mg/L was higher in the model-based treatment group compared to the standard treatment group (80.8% vs 59.3%). Conclusion: The use of individualized pharmacogenetic-guided INH dosage regimens that incorporate NAT2 genotype and body weight may help to ensure achievement of therapeutic concentrations of INH in the TB patients. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | DOVE MEDICAL PRESS LTD | - |
dc.title | A proposal for an individualized pharmacogenetic-guided isoniazid dosage regimen for patients with tuberculosis | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, Hyun | - |
dc.identifier.doi | 10.2147/DDDT.S87131 | - |
dc.identifier.scopusid | 2-s2.0-84943188575 | - |
dc.identifier.wosid | 000362183000001 | - |
dc.identifier.bibliographicCitation | DRUG DESIGN DEVELOPMENT AND THERAPY, v.9, pp.5433 - 5438 | - |
dc.relation.isPartOf | DRUG DESIGN DEVELOPMENT AND THERAPY | - |
dc.citation.title | DRUG DESIGN DEVELOPMENT AND THERAPY | - |
dc.citation.volume | 9 | - |
dc.citation.startPage | 5433 | - |
dc.citation.endPage | 5438 | - |
dc.type.rims | ART | - |
dc.type.docType | 정기학술지(Article(Perspective Article포함)) | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | GENOTYPE | - |
dc.subject.keywordPlus | NAT2 | - |
dc.subject.keywordPlus | DRUGS | - |
dc.subject.keywordAuthor | tuberculosis | - |
dc.subject.keywordAuthor | pharmacogenomics | - |
dc.subject.keywordAuthor | NAT2 genotype | - |
dc.subject.keywordAuthor | INH regimen | - |
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