Liver Fibrosis Impairs Hepatic Pharmacokinetics of Liver Transplant Drugs in the Rat Model

This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl4-induced fibrotic perfused rat livers and the res...

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Veröffentlicht in:	DRUG METABOLISM AND PHARMACOKINETICS 2010-01, Vol.25 (5), p.442-449
Hauptverfasser:	Zou, Yu-Hong, Liu, Xin, Khlentzos, Alexander M., Asadian, Peyman, Li, Peng, Thorling, Camilla A., Robertson, Thomas A., Fletcher, Linda M., Crawford, Darrell H.G., Roberts, Michael S.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Bile Ducts, Intrahepatic - drug effects Bile Ducts, Intrahepatic - physiopathology Carbon Tetrachloride - pharmacology Extracellular Space - drug effects furosemide Furosemide - metabolism Furosemide - pharmacokinetics hepatic pharmacokinetics Liver - drug effects Liver - metabolism Liver - pathology Liver - physiopathology Liver Cirrhosis - chemically induced Liver Cirrhosis - metabolism Liver Cirrhosis - physiopathology liver fibrosis Liver Transplantation Male metoprolol Metoprolol - metabolism Metoprolol - pharmacokinetics Models, Biological omeprazole Omeprazole - metabolism Omeprazole - pharmacokinetics Organ Size - drug effects Oxygen Consumption - drug effects Pharmaceutical Preparations - metabolism Pharmacokinetics propranolol Propranolol - metabolism Propranolol - pharmacokinetics Rats Rats, Wistar spironolactone Spironolactone - metabolism Spironolactone - pharmacokinetics Transplantation Conditioning Water - metabolism
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Beschreibung
Zusammenfassung:	This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl4-induced fibrotic perfused rat livers and the results were compared to those in normal rat liver. Drug outflow fraction-time profiles were obtained after bolus injection into a single-pass-perfused normal or fibrotic rat liver. The pharmacokinetic parameters were estimated using previously developed barrier-limited and space-distributed models. The results showed a marked increase in the liver fibrosis index for CCl4-treated rats compared to controls (p
ISSN:	1347-4367 1880-0920
DOI:	10.2133/dmpk.DMPK-10-RG-031