Pharmacokinetic Study of Isoniazid and Rifampicin in Patients Suffering from Antitubercular Drugs (ATD) Induced Hepatotoxicity

Rath, Rishi; Tevatia, Siddharth

doi:10.4172/jbb.1000312

Cited by 2 publications

(1 citation statement)

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“…Similar findings were reported by the Rath and Tevatia study, where the authors observed increased Cmax and decreased clearance of isoniazid in patients suffering from ATD-induced hepatotoxicity, indicating that there was delayed elimination of isoniazid as compared to patients without hepatotoxicity. [ 15 ] Another study by Acocella et al . reported a rise in isoniazid levels in the presence of rifampicin after seven days of coadministration in liver injury patients.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Assessment of Isoniazid and Acetylisoniazid in Carbon Tetrachloride-Induced Liver Injury Model in Wistar Rats

Sharma

Anand

Verma

et al. 2023

Journal of Pharmacy and Bioallied Sciences

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Background: 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’s reintroduction regimen variations exist because of the scarcity of robust preclinical evidence on ATT drug metabolism. Objective: 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 (CCl4) and preclinical drug-induced liver injury (DILI) model induced with CCl4 + anti-Tuberculosis (TB) drugs together. Materials and Methods: Thirty rats were used for the experiment and were divided into five groups. All rats were administered a single 0.5 ml/kg CCl4 intraperitoneal injection on day 0 to induce an animal model of DILI. Group I rats received CCl4 alone. Groups II–V 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. Results: Three-week ATT administration sustained the CCl4-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 CCl4 + H group, respectively (P < 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 CCl4 + Isoniazid+Rifampicin+Pyrazinamide (HRZ) group compared with the CCl4 + H group (P < 0.05). Biochemical, histological, and antioxidant changes were consistent with the new liver injury model’s development. Conclusion: Rifampicin almost doubles up the isoniazid and AcINH exposure, in presence if DILI.

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Section: Discussionmentioning

confidence: 99%