Korean J Hepatol.
2002 Sep;8(3):277-287.
Relationship of Propranolol Pharmacokinetic Parameters with Portosystemic Shunt in CCl4-induced cirrhotic Rats
- Affiliations
-
- 1Research Institute of Digestive Disease, Hanyang University Collage of Medicine, Seoul, Korea. minho@hanyang.ac.kr
- 2Department of Nuclear Medicine, Hanyang University Collage of Medicine, Seoul, Korea.
- 3Department of Pharmacology, Hanyang University Collage of Medicine, Seoul, Korea.
Abstract
- BACKGROUND: This study was designed to determine the relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced cirrhotic rats. METHODS: Cirrhotic rats(n=6) were induced by intramuscular injection of CCl4 in olive oil(two time per weeks) for 12 weeks. Controls (n=6) were injected intramuscularly with the same dose of olive oil for 12 weeks. We evaluated the amount of portosystemic shunt by thallium-201 per rectal scintigraphy. After intravenous bolus injection of propranolol (2mg/kg) to rats, the serum propranolol concentrations were analyzed by a HPLC-fluorimetric detector system. Pharmacokinetic parameters such as C0, AUC, t(1/2(beta)), and CLp were determined in each group. Then, a small amount of heptic tissue was obtained and subjected to determination of the hepatic collagen content by quantitating 4-hydroxyproline and were inspected by microscope after hematoxylin and eosin stain. RESULTS: In liver biopsy, liver fibrosis progressed in CCl4-induced cirrhotic rats. The serum concentrations of propranolol were significantly (p < 0.01) elevated in CCl4-induced cirrhotic rats. Mean amount of 4-hydroxyproline, mean H/L ratio, and mean AUC in CCl4-induced cirrhotic rats was significantly (p < 0.01) higher than that in control rats. There was a relationship between AUC, H/L ratio, and amount of 4-hydroxyproline. CONCLUSION: H/L ratio may help in the selection of drug dosage (especially blood flow dependent drug) in pre-clinical studies for chronic liver disease during the drug development process.
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Changes of Propranolol Pharmacokinetic Parameters According to Hepatic Fibrotic Severity in CCl4-Treated Rats
- Non-cirrhotic Hyperammonemic Encephalopathy with Portosystemic Shunt
- A pediatric case of portosystemic shunt presenting hypoxemia with brain abscess in an emergency department
- Intrahepatic Portosystemic Venous Shunt Presenting as a Cystic Mass in a Patient without Liver Cirrhosis: A Case Report
- Endovascular Closure Resolves Trimethylaminuria Caused by Congenital Portosystemic Shunts
