Relationship of Propranolol Pharmacokinetic Parameters with Portosystemic Shunt in CCl4-induced cirrhotic Rats.
- Author:
Dong Hee KOH
1
;
Geun Tae PARK
;
Jung Mi KIM
;
Yeong Seop YUN
;
Sung Hee LEE
;
Dong Uk KIM
;
Jin Bae KIM
;
Yun Yung CHOI
;
Ju Seop KANG
;
Ho Soon CHOI
;
Joon Soo HAHM
;
Min Ho LEE
Author Information
1. Research Institute of Digestive Disease, Hanyang University Collage of Medicine, Seoul, Korea. minho@hanyang.ac.kr
- Publication Type:Original Article ; English Abstract
- Keywords:
Propranolol;
Liver cirrhosis;
Pharmacokinetic parameter;
Thallium scintigraphy
- MeSH:
Animals;
Carbon Tetrachloride Poisoning/*complications;
Chromatography, High Pressure Liquid;
English Abstract;
Liver Cirrhosis, Experimental/*metabolism/physiopathology;
Portal System/physiopathology;
Propranolol/*pharmacokinetics;
Rats;
Rats, Sprague-Dawley;
Thallium Radioisotopes/diagnostic use
- From:The Korean Journal of Hepatology
2002;8(3):277-287
- CountryRepublic of Korea
- Language:Korean
-
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.
