Effects of albumin and alpha-1 acid glycoprotein on elimination of prazosin and antipyrine in the isolated perfused rat liver.
This study was undertaken to investigate the effect of albumin and alpha-1 acid glycoprotein on the elimination of drugs with a low extraction ratio in the isolated perfused rat liver. The unbound clearance of prazosin increased 69% after the addition of 14 mg/ml of albumin to the perfusate whereas the unbound clearance decreased by 51% after the addition of 0.85 mg/ml of alpha-1 acid glycoprotein. The clearance of antipyrine, a compound not bound to albumin or alpha-1 acid glycoprotein, increased 28% in the presence of albumin but was not altered in the presence of alpha-1 acid glycoprotein. These results suggest that albumin has the ability to enhance the elimination of drugs both bound and not bound to albumin. This effect was found not to be related to pH changes across the liver or to the oncotic pressure effect of albumin. Alpha-1 acid glycoprotein, on the other hand, seems to be able to decrease the elimination of drugs which bind to it, but has no effect on drugs that are not bound.
D000818:Animals; D000983:Antipyrine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D009961:Orosomucoid / Q000494:pharmacology*; D010477:Perfusion; D011224:Prazosin / Q000378:metabolism*; D011485:Protein Binding; D011799:Quinazolines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000494:pharmacology*
D009961:Orosomucoid; D011799:Quinazolines; D012709:Serum Albumin; D000983:Antipyrine; D011224:Prazosin