PMID: 3746632Feb 1, 1986Paper

Effect of albumin on hepatic uptake of warfarin in normal and analbuminemic mutant rats: analysis by multiple indicator dilution method

Journal of Pharmacokinetics and Biopharmaceutics
S C TsaoM Hanano

Abstract

Multiple indicator dilution studies of warfarin uptake were carried out on isolated perfused rat livers in the presence and absence of bovine serum albumin (BSA) in the perfusate using normal rats and Nagase analbuminemic rats (NAR). A distributed model was fitted to the dilution data and estimates of influx, efflux, and sequestration rate constants were obtained. In both groups of rats, the intrinsic clearance for unidirectional hepatic uptake (CLint,influx) of warfarin in the presence of 1.6 g/dl BSA was approximately 37-45% of that in the absence of BSA, while the unbound fraction of warfarin with 1.6 g/dl BSA in the perfusate was only 4.2% of that in the absence of BSA. Thus the degree of BSA-induced reduction of the value of CLint,influx and that of the unbound fraction are different. From these observations, it was found that the hepatic uptake of warfarin is not driven solely by the unbound concentration of warfarin, supporting the recent concepts of albumin-mediated transport for tightly albumin bound ligands as reported by Ockner et al. In addition, the fact that the same hepatic uptake mechanism of warfarin was also observed in NAR suggested that the hepatic uptake of warfarin may not necessarily require a special alb...Continue Reading

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Citations

Apr 1, 1993·European Journal of Drug Metabolism and Pharmacokinetics·J I TroconizD Fos
Feb 1, 1997·Clinical and Experimental Pharmacology & Physiology·J A O'BrienR L Nation
Sep 1, 1992·Epilepsia·E M CornfordR D Sofia
Nov 19, 1997·The Journal of Pharmacy and Pharmacology·G D Mellick, M S Roberts
Jun 13, 1998·The Journal of Pharmacy and Pharmacology·T MurakamiM Takano
Apr 1, 1988·Journal of Pharmacokinetics and Biopharmaceutics·S C TsaoM Hanano
Apr 1, 1992·Journal of Pharmacokinetics and Biopharmaceutics·J M Díaz-GarcíaM Rowland
Jul 1, 1995·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·K S PangC A Goresky
Jan 1, 1992·Cancer Chemotherapy and Pharmacology·E M CornfordJ W Paxton
Feb 1, 1987·Journal of Pharmacokinetics and Biopharmaceutics·S MiyauchiM Hanano
Oct 26, 2013·Journal of Cardiovascular Pharmacology·Patricia Sanwald-DucrayLudger Banken
Sep 8, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jae H ChangJodie Pang
Aug 12, 2018·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·C M Bowman, L Z Benet
Jan 1, 1996·Annales Françaises D'anesthèsie Et De Rèanimation·Y Ozier
Sep 15, 1989·Biochemical Pharmacology·E L VansterkenburgL H Janssen
Aug 1, 1988·Journal of Pharmaceutical Sciences·S MiyauchiM Hanano

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