Effect of altered albumin concentrations on elimination of unbound prazosin in vivo in the rat and in the isolated perfused rat liver

Svein Øie, Yea-Huei Kao

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Abstract

Albumin is known to affect the intrinsic clearance of many compounds in the isolated perfused rat liver, but little is known of its effect in vivo. The influence of decreased albumin concentrations on clearance of unbound prazosin and intrinsic clearance of prazosin was therefore studied in vivo in rats that had undergone plasmapheresis. An approximate 30% reduction in the plasma albumin concentration was achieved in animals not given plasma expanders and an approximate 50% reduction was achieved in animals given Ficol 70 as a plasma expander. No differences were seen in the intrinsic clearances or in the clearances of unbound prazosin between control animals and plasmapheretic animals. The reason for this lack of effect is apparent from parallel studies in isolated perfused rat livers. An increase in the clearance of unbound prazosin of 27% was seen when the albumin concentration was increased from 0 to 30 μM, and of 49% when the concentration of albumin was increased to 90 μM, with no further increase at higher albumin concentration. These results, therefore, suggest that changes in the albumin plasma concentrations normally encountered clinically may have little effect on the intrinsic elimination of drugs.

Original languageEnglish
Pages (from-to)948-951
Number of pages4
JournalJournal of Pharmaceutical Sciences
Volume77
Issue number11
DOIs
Publication statusPublished - 1988 Jan 1

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Prazosin
Albumins
Liver
Serum Albumin
Plasmapheresis
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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title = "Effect of altered albumin concentrations on elimination of unbound prazosin in vivo in the rat and in the isolated perfused rat liver",
abstract = "Albumin is known to affect the intrinsic clearance of many compounds in the isolated perfused rat liver, but little is known of its effect in vivo. The influence of decreased albumin concentrations on clearance of unbound prazosin and intrinsic clearance of prazosin was therefore studied in vivo in rats that had undergone plasmapheresis. An approximate 30{\%} reduction in the plasma albumin concentration was achieved in animals not given plasma expanders and an approximate 50{\%} reduction was achieved in animals given Ficol 70 as a plasma expander. No differences were seen in the intrinsic clearances or in the clearances of unbound prazosin between control animals and plasmapheretic animals. The reason for this lack of effect is apparent from parallel studies in isolated perfused rat livers. An increase in the clearance of unbound prazosin of 27{\%} was seen when the albumin concentration was increased from 0 to 30 μM, and of 49{\%} when the concentration of albumin was increased to 90 μM, with no further increase at higher albumin concentration. These results, therefore, suggest that changes in the albumin plasma concentrations normally encountered clinically may have little effect on the intrinsic elimination of drugs.",
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T1 - Effect of altered albumin concentrations on elimination of unbound prazosin in vivo in the rat and in the isolated perfused rat liver

AU - Øie, Svein

AU - Kao, Yea-Huei

PY - 1988/1/1

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N2 - Albumin is known to affect the intrinsic clearance of many compounds in the isolated perfused rat liver, but little is known of its effect in vivo. The influence of decreased albumin concentrations on clearance of unbound prazosin and intrinsic clearance of prazosin was therefore studied in vivo in rats that had undergone plasmapheresis. An approximate 30% reduction in the plasma albumin concentration was achieved in animals not given plasma expanders and an approximate 50% reduction was achieved in animals given Ficol 70 as a plasma expander. No differences were seen in the intrinsic clearances or in the clearances of unbound prazosin between control animals and plasmapheretic animals. The reason for this lack of effect is apparent from parallel studies in isolated perfused rat livers. An increase in the clearance of unbound prazosin of 27% was seen when the albumin concentration was increased from 0 to 30 μM, and of 49% when the concentration of albumin was increased to 90 μM, with no further increase at higher albumin concentration. These results, therefore, suggest that changes in the albumin plasma concentrations normally encountered clinically may have little effect on the intrinsic elimination of drugs.

AB - Albumin is known to affect the intrinsic clearance of many compounds in the isolated perfused rat liver, but little is known of its effect in vivo. The influence of decreased albumin concentrations on clearance of unbound prazosin and intrinsic clearance of prazosin was therefore studied in vivo in rats that had undergone plasmapheresis. An approximate 30% reduction in the plasma albumin concentration was achieved in animals not given plasma expanders and an approximate 50% reduction was achieved in animals given Ficol 70 as a plasma expander. No differences were seen in the intrinsic clearances or in the clearances of unbound prazosin between control animals and plasmapheretic animals. The reason for this lack of effect is apparent from parallel studies in isolated perfused rat livers. An increase in the clearance of unbound prazosin of 27% was seen when the albumin concentration was increased from 0 to 30 μM, and of 49% when the concentration of albumin was increased to 90 μM, with no further increase at higher albumin concentration. These results, therefore, suggest that changes in the albumin plasma concentrations normally encountered clinically may have little effect on the intrinsic elimination of drugs.

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