Propranolol metabolism by isolated hepatocytes from normal and cirrhotic rat livers: the effect of albumin.
Several recent reports have shown that the hepatic uptake and subsequent elimination of some substrates is faster in the presence of albumin than in its absence, as if some of the substrate bound to albumin was also available for uptake. In the present study, we examined the effect of albumin on the clearance of propranolol by isolated rat hepatocyte suspensions. The clearance of total drug decreased progressively as albumin concentration increased. There was also a progressive decrease in the free fraction of propranolol and the net result was an increase in the clearance of unbound drug (+50% at 40 g/L albumin). This increase was not due to an oncotic pressure effect of albumin, nor to the presence of fatty acids bound to albumin. The clearance of propranolol by isolated hepatocytes from cirrhotic rats was decreased compared with controls (-50%), and albumin also increased propranolol free clearance, albeit to a lesser extent than in control animals. Our results indicate that albumin facilitates the elimination of propranolol by hepatocytes, possibly because of surface-mediated catalysis of the albumin-propranolol complexes.
Gariepy
L
L
Department of Medicine, Centre de recherche clinique André-Viallet, Hôpital Saint-Luc, Montréal, Quebec, Canada.
Fenyves
D
D
Petit
J L
JL
Raymond
G
G
Villeneuve
J P
JP
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D002251:Carbon Tetrachloride; D002470:Cell Survival; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D003012:Microbial Collagenase / Q000378:metabolism; D010477:Perfusion; D011433:Propranolol / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains
D000418:Albumins; D011433:Propranolol; D002251:Carbon Tetrachloride; D003012:Microbial Collagenase