Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats
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Swati Sharma
and
Dibyajyoti Banerjee
Abstract
Objectives
Preclinical evidence is needed to assess drug-metabolite behaviour in compromised liver function for developing the best antitubercular treatment (ATT) re-introduction regimen in drug-induced liver injury (DILI). The pharmacokinetic behavior of rifampicin (RMP) and its active metabolite des-acetyl-rifampicin (DARP) in DILI’s presence is unknown. To study the pharmacokinetic behavior of RMP and DARP in the presence of carbon tetrachloride (CCl4) plus ATT-DILI in rats.
Methods
Thirty rats used in the experiment were divided equally into six groups. We administered a single 0.5 mL/kg CCl4 intraperitoneal injection in all rats. Groups II, III, IV, and V were started on daily oral RMP alone, RMP plus isoniazid (INH), RMP plus pyrazinamide (PZA), and the three drugs INH, RMP, and PZA together, respectively, for 21-days subsequently. Pharmacokinetic (PK) sampling was performed at 0, 0.5, 1, 3, 6, 12, and 24 h post-dosing on day 20. We monitored LFT at baseline on days-1, 7, and 21 and sacrificed the rats on the last day of the experiment.
Results
ATT treatment sustained the CCl4-induced liver injury changes. A significant rise in mean total bilirubin levels was observed in groups administered rifampicin. The triple drug combination group demonstrated 1.43- and 1.84-times higher area-under-the-curve values of RMP (234.56±30.66 vs. 163.55±36.14 µg h/mL) and DARP (16.15±4.50 vs. 8.75±2.79 µg h/mL) compared to RMP alone group. Histological and oxidative stress changes supported underlying liver injury and PK alterations.
Conclusions
RMP metabolism inhibition by PZA, more than isoniazid, was well preserved in the presence of underlying liver injury.
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Ethical approval: Study protocol was approved by the Animal Ethics Committee (761/IAEC/110-C) and all experiments complied with the ARRIVE(Animal Research: Reporting of In Vivo Experiments) 2.0 guidelines.
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Informed consent: Informed consent was not required in this study.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Research funding: None declared.
References
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/jcim-2023-0235).
© 2023 Walter de Gruyter GmbH, Berlin/Boston
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Articles in the same Issue
- Frontmatter
- Reviews
- Markhamia lutea leaves aqueous and ethanolic extract with curative anti-inflammatory activity attenuates paclitaxel toxicity in rat’s intestine
- Does hydrotherapy influence plasma glucose levels in type 2 diabetes? – A scoping review
- Comparative effectiveness is the common denominator in health services research: experimental effects are promising, real-world effects are compelling
- Research Articles
- Hydroethanolic extract of Piliostigma thonningii leaves extenuates the severity of diarrhoea in female Wistar rats
- Pharmacokinetic assessment of rifampicin and des-acetyl rifampicin in carbon tetrachloride induced liver injury model in Wistar rats
- Antipyretic activity of the hydro-alcoholic extract of Artemisia absinthium L. as a standalone and as an adjuvant with barley water against yeast-induced pyrexia in albino Wistar rats
- Selenium prevented renal tissue damage in lipopolysaccharide-treated rats
- Preliminary data on cytotoxicity and functional group assessment of a herb–mineral combination against colorectal carcinoma cell line
- Oral intake of collagen hydrolysate from mackerel scad (Decapterus macarellus) attenuates skin photoaging by suppressing the UVB-induced expression of MMP-1 and IL-6
- Pentaclethra macrophylla leaves reduce blood glucose level, improve sexual behavior and modulate critical enzymes associated with diabetes-erectile dysfunction morbidity in rats
- Anti-melanoma and antioxidant properties of the methanol extract from the leaves of Phragmenthera capitata (Spreng.) Balle and Globimetula braunii (Engl.) Van Tiegh
- The assessment of the mechanism of action of lauric acid in the context of oral cancer through integrative approach combining network pharmacology and molecular docking technology
- Therapeutic potential of flavonoids in ovalbumin induced asthma in mice model
- The effects of pioglitazone and rosiglitazone on liver function in hypothyroid rats
- Effect of ozone gas on viral kinetics and liver histopathology in hepatitis C patients
