title: [Relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced cirrhotic rats].
abstract: OBJECTIVE
  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, 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Institute of Digestive Disease, Hanyang University Collage of Medicine, Seoul, Korea.
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Koh
authors.forename: Geun Tae
authors.initials: GT
authors.lastname: Park
authors.forename: Jung Mi
authors.initials: JM
authors.lastname: Kim
authors.forename: Yeong Seop
authors.initials: YS
authors.lastname: Yun
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Dong Uk
authors.initials: DU
authors.lastname: Kim
authors.forename: Jin Bae
authors.initials: JB
authors.lastname: Kim
authors.forename: Yun Yung
authors.initials: YY
authors.lastname: Choi
authors.forename: Ju Seop
authors.initials: JS
authors.lastname: Kang
authors.forename: Ho Soon
authors.initials: HS
authors.lastname: Choi
authors.forename: Joon Soo
authors.initials: JS
authors.lastname: Hahm
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000150:complications*; D002851:Chromatography, High Pressure Liquid; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D011168:Portal System / Q000503:physiopathology; D011433:Propranolol / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013794:Thallium Radioisotopes
chemical_list: D013794:Thallium Radioisotopes; D011433:Propranolol