{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:02:32Z","timestamp":1787169752426,"version":"build-2736575974"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7]]},"abstract":"\n A\n BSTRACT<\/jats:sc>\n <\/jats:title>\n \n Background:<\/jats:title>\n N-acetyl transferase 2 (NAT2) polymorphism testing could not see the light of success as a biomarker tool in tuberculosis management. Additionally, the antitubercular treatment (ATT) drug\u2019s reintroduction regimen variations exist because of the scarcity of robust preclinical evidence on ATT drug metabolism.<\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n \n The experiment was planned to understand the pharmacokinetic (PK) behavior of isoniazid and acetylisoniazid (AcINH) in a Wistar rat model of acute liver injury induced by carbon tetrachloride (CCl\n 4<\/jats:sub>\n ) and preclinical drug-induced liver injury (DILI) model induced with CCl\n 4<\/jats:sub>\n + anti-Tuberculosis (TB) drugs together.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n \n Thirty rats were used for the experiment and were divided into five groups. All rats were administered a single 0.5 ml\/kg CCl\n 4<\/jats:sub>\n intraperitoneal injection on day 0 to induce an animal model of DILI. Group I rats received CCl\n 4<\/jats:sub>\n alone. Groups II\u2013V were started on additional gavage feedings of isoniazid (H) alone, H plus rifampicin (R), H plus pyrazinamide (Z), and H, R, and Z together, respectively, daily for 21 days subsequently. Isoniazid and AcINH PK assessment was accomplished on day 20 of continuous once-daily dosing. Liver function test (LFT) monitoring was done at baseline on days 1, 7, and 21. On the last day of experiments, all experimental rats were sacrificed.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Three-week ATT administration sustained the CCl\n 4<\/jats:sub>\n -induced LFT changes. Area under the curve (AUC) values for isoniazid and AcINH were found to be 2.24 and 1.69 times higher in the H + R group compared with the CCl\n 4<\/jats:sub>\n + H group, respectively (\n P<\/jats:italic>\n < 0.05). Isoniazid and AcINH maximum concentration (Cmax) reached the highest, while isoniazid clearance reached the lowest in the H + R group. AcINH AUC increased by double in the CCl\n 4<\/jats:sub>\n + Isoniazid+Rifampicin+Pyrazinamide (HRZ) group compared with the CCl\n 4<\/jats:sub>\n + H group (\n P<\/jats:italic>\n < 0.05). Biochemical, histological, and antioxidant changes were consistent with the new liver injury model\u2019s development.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Rifampicin almost doubles up the isoniazid and AcINH exposure, in presence if DILI.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/jpbs.jpbs_320_23","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T02:00:48Z","timestamp":1692151248000},"page":"139-145","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetic Assessment of Isoniazid and Acetylisoniazid in Carbon Tetrachloride-Induced Liver Injury Model in Wistar Rats"],"prefix":"10.4103","volume":"15","author":[{"given":"Swati","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 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