{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:02:15Z","timestamp":1784538135999,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The relationship between age and isoniazid acetylation phenotype remains insufficiently characterized, particularly in elderly populations, where pharmacokinetic variability and susceptibility to toxicity may be increased. This study aimed to characterize isoniazid acetylation phenotypes in elderly Tunisian patients using a phenotypic index and to assess its clinical implications. A retrospective study was conducted on 476 Tunisian tuberculosis patients treated with isoniazid between 2019 and 2024. Plasma concentrations at 3 h post\u2010dose (C\n                    <jats:sub>3<\/jats:sub>\n                    ) were used to determine the acetylation index (I\n                    <jats:sub>3<\/jats:sub>\n                    ) and classify patients as rapid acetylators (RAs) or slow acetylators (SAs). Associations between acetylation phenotype, C\n                    <jats:sub>3,<\/jats:sub>\n                    dose adjustments, adverse events, and clinical variables were assessed using non\u2010parametric and categorical statistical tests. Slow acetylators represented 68.1% of the cohort and were associated with significantly higher isoniazid exposure and a greater proportion of supra\u2010therapeutic concentrations. Overall, 66.0% of patients exhibited supra\u2010therapeutic concentrations. Acetylator status significantly influenced dose adjustment requirements, with 89.2% of SAs requiring modification, mainly dose reductions. Adverse events occurred in 34.9% of patients and were significantly more frequent in SAs compared with RAs (44.1% vs 15.1%,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;.001). No significant association was observed between age and acetylation phenotype or plasma exposure, although age was associated with adverse events. Renal function showed no significant correlation with acetylation status or exposure. The high interindividual variability observed supports the use of phenotypic assessment (I\n                    <jats:sub>3<\/jats:sub>\n                    ) to guide individualized dosing, particularly in settings where NAT2 genotyping is not routinely available. Prospective studies integrating pharmacogenetic and pharmacokinetic approaches are warranted to refine precision therapy in this high\u2010risk population.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70217","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T14:24:59Z","timestamp":1780323899000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acetylation Variability in Elderly Tunisians: Implications for Isoniazid Dose Individualization"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3172-5108","authenticated-orcid":false,"given":"Yasmine","family":"Khefacha","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy of Monastir University of Monastir  Monastir Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syrine","family":"Ben\u2010Hammamia","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Ben Sassi","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khouloud","family":"Ferchichi","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Daldoul","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanene","family":"El Jebari","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Zouari","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam","family":"Salouage","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rim","family":"Charfi","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riadh","family":"Daghfous","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emna","family":"Gaies","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Trabelsi","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Department of Clinical Pharmacology National Centre Chalbi Belkahia of Pharmacovigilance  Tunis Tunisia"},{"name":"Faculty of Medicine of Tunis University of Tunis El Manar  Tunis Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_2_10_2_1","article-title":"En Clair | Tuberculose : l\u2019\u00e9pid\u00e9mie est\u2010elle en train de repartir \u00e0 la hausse ?","author":"Rejichi D","year":"2024","journal-title":"Inkyfada"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2023.2196401"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083881"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201038716\u20103"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710790416326"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2021.1839413"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2021.01.033"},{"key":"e_1_2_10_9_1","volume-title":"Proposed working definition of an older person in Africa for the MDS Project [Internet]","author":"World Health Organization","year":"2002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.4172\/2325-9604.1000177"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e07532"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1813"},{"key":"e_1_2_10_13_1","first-page":"753","article-title":"La pharmacocin\u00e9tique de l'isoniazide dans la race blanche","volume":"1","author":"Vivien J","year":"1973","journal-title":"Rev Fr Mal Respir"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010022\u201003362\u20107"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1037814"},{"key":"e_1_2_10_16_1","volume-title":"StatPearls [Internet]","author":"Badrinath M","year":"2024"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2016.26"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00546707"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000062"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2016.07.014"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.revmed.2023.04.165"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmr.2014.11.061"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1980.tb01735.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00544374"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00541539"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.5414\/CP201957"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-25787-7"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2020.09.009"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41999\u2010021\u201000481\u20109"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00543329"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17082620"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eimc.2017.10.018"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70217","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70217","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:06:11Z","timestamp":1784534771000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/jcph.70217"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70217","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70217"}}