PMID- 3746632
OWN - NLM
STAT- MEDLINE
DCOM- 19861001
LR  - 20191022
IS  - 0090-466X (Print)
IS  - 0090-466X (Linking)
VI  - 14
IP  - 1
DP  - 1986 Feb
TI  - Effect of albumin on hepatic uptake of warfarin in normal and analbuminemic 
      mutant rats: analysis by multiple indicator dilution method.
PG  - 51-64
AB  - 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 albumin receptor 
      on the hepatocyte surface.
FAU - Tsao, S C
AU  - Tsao SC
FAU - Sugiyama, Y
AU  - Sugiyama Y
FAU - Sawada, Y
AU  - Sawada Y
FAU - Nagase, S
AU  - Nagase S
FAU - Iga, T
AU  - Iga T
FAU - Hanano, M
AU  - Hanano M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pharmacokinet Biopharm
JT  - Journal of pharmacokinetics and biopharmaceutics
JID - 0357115
RN  - 0 (Serum Albumin)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 5Q7ZVV76EI (Warfarin)
SB  - IM
MH  - Animals
MH  - Erythrocytes/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Liver/*metabolism
MH  - Male
MH  - Models, Biological
MH  - Protein Binding
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Rats, Mutant Strains
MH  - Serum Albumin/*deficiency
MH  - Serum Albumin, Bovine/metabolism
MH  - Warfarin/*metabolism
EDAT- 1986/02/01 00:00
MHDA- 1986/02/01 00:01
CRDT- 1986/02/01 00:00
PHST- 1986/02/01 00:00 [pubmed]
PHST- 1986/02/01 00:01 [medline]
PHST- 1986/02/01 00:00 [entrez]
AID - 10.1007/BF01059283 [doi]
PST - ppublish
SO  - J Pharmacokinet Biopharm. 1986 Feb;14(1):51-64. doi: 10.1007/BF01059283.