| Autor: |
Dong Hee, Koh, 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 |
| Rok vydání: |
2002 |
| Předmět: |
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| Zdroj: |
Taehan Kan Hakhoe chi = The Korean journal of hepatology. 8(3) |
| ISSN: |
1226-0479 |
| Popis: |
This study was designed to determine the relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced cirrhotic rats.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, t1/2(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.In liver biopsy, liver fibrosis progressed in CCl4-induced cirrhotic rats. The serum concentrations of propranolol were significantly (p0.01) 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 (p0.01) higher than that in control rats. There was a relationship between AUC, H/L ratio, and amount of 4-hydroxyproline.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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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