ArticleEuropean journal of drug metabolism and pharmacokinetics2017
Antifibrotic Effects of Carvedilol and Impact of Liver Fibrosis on Carvedilol Pharmacokinetics in a Rat model.
Article in European journal of drug metabolism and pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Advances in pharmacological interventions for hepatic fibrosis: from pathogenic mechanisms to novel therapeutic targets.Annals of medicine · 2026Review
- Carvedilol decreases hepatic vascular resistance by reducing fibrogenesis and reversing endothelial dysfunction in cirrhotic rats.JHEP reports : innovation in hepatology · 2026Article
- Dual therapy with vildagliptin and sacubitril/valsartan alleviates portal hypertension and inhibits soluble epoxide hydrolase in cirrhotic rats.World journal of gastroenterology · 2025Article
- Neuroimmunomodulation of adrenoblockers during liver cirrhosis: modulation of hepatic stellate cell activity.Annals of medicine · 2023Review
- Article
- Hepatoprotective Role of Carvedilol against Ischemic Hepatitis Associated with Acute Heart Failure via Targeting miRNA-17 and Mitochondrial Dynamics-Related Proteins: An In Vivo and In Silico Study.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Exploring the Potential Chemoprophylactic Role of Carvedilol for Hepatocellular Carcinoma.Gastroenterology & hepatology · 2022Article
- Green Synthesis of Silymarin-Chitosan Nanoparticles as a New Nano Formulation with Enhanced Anti-Fibrotic Effects against Liver Fibrosis.International journal of molecular sciences · 2022Article
- Protective Effect of Curcumin against Doxazosin- and Carvedilol-Induced Oxidative Stress in HepG2 Cells.Oxidative medicine and cellular longevity · 2022Article
- Carvedilol improves liver cirrhosis in rats by inhibiting hepatic stellate cell activation, proliferation, invasion and collagen synthesis.Molecular medicine reports · 2019Article
- Comparative Pharmacokinetic Study of Taxifolin after Oral Administration of Fructus Polygoni Orientalis Extract in Normal and Fibrotic Rats by UPLC-MS/MS.Evidence-based complementary and alternative medicine : eCAM · 2019Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesCarvedilol is a drug of choice in treatment of portal hypertension. The present study was designed to elucidate the potential role of antifibrotic effects of carvedilol in improving hepatic efficiency and the carvedilol oral pharmacokinetic changes during induction of liver fibrosis.
methodsRats were given CCl4 (1 ml/kg, intraperitoneal) twice weekly for 6 weeks and/or co-treated with carvedilol (10 mg/kg, orally) three times weekly on alternating days. Indocyanine green (ICG) clearance test was used as a modality for the measurement of hepatic blood flow. In addition, assessment of serum albumin as a marker of synthetic capacity and immunohistochemical staining of P-glycoprotein (P-gp) expression as a marker of metabolic capacity were done. Furthermore, hydroxyproline and TGF-β1 were detected as markers of liver fibrosis.
resultsThe area under plasma concentration-time curve of a single dose of carvedilol was significantly increased, associated with decreased the clearance in rats intoxicated with CCl4 compared to control group. Carvedilol co-treatment in CCl4-intoxicated rats for 6 weeks significantly counteracted the changes in hepatotoxicity markers and histopathological lesions induced by CCl4. In addition, there were no significant alterations in carvedilol pharmacokinetics between control and CCl4-intoxicated rats. Furthermore, carvedilol treatment restored liver efficiency, including synthetic and metabolic capacity as well as hepatic blood flow.
conclusionThe present study provides evidence underlying the antifibrotic effects of carvedilol and enhancement of hepatic efficiency. In addition, the pharmacokinetic parameters of a single dose of carvedilol are altered in liver fibrosis, manifested as delayed clearance. This was attributed to the reduction of both hepatic blood flow and CYP2D6 expression in the liver. Carvedilol co-treatment in CCl4-intoxicated rats for 6 weeks recovered its pharmacokinetic profile, which is mainly attributed to the impact of pharmacodynamic antifibrotic effects of carvedilol on its own kinetics.
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