Relationship of Propranolol Pharmacokinetic Parameters with Portosystemic Shunt in CCl4-induced cirrhotic Rats / 대한간학회지
The Korean Journal of Hepatology
;
: 277-287, 2002.
Article
Dans Coréen
| WPRIM
| ID: wpr-117151
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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Système porte
/
Propranolol
/
Résumé en anglais
/
Intoxication au tétrachlorure de carbone
/
Radio-isotopes du thallium
/
Chromatographie en phase liquide à haute performance
/
Rat Sprague-Dawley
/
Cirrhose expérimentale
Limites du sujet:
Animaux
langue:
Coréen
Texte intégral:
The Korean Journal of Hepatology
Année:
2002
Type:
Article
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