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Pharmaceutisch Weekblad

, Volume 9, Issue 2, pp 65–74 | Cite as

The influence of binding to albumin and α1-acid glycoprotein on the clearance of drugs by the liver

  • Dirk K. F. Meijer
  • Peter Van Der Sluijs
Pharmacokinetics and Organ Dysfunction

Abstract

The liver is a major site for synthesis and catabolism of plasma proteins. Albumin has various binding sites for anionic drugs,α1acid glycoprotein possesses a single binding site for cationic drugs. In spite of extensive protein binding, the liver can efficiently remove drags from the circulation. Intrahepatic dissociation of the drag-protein complex may involve dissociation-limited debinding under non-equilibrium conditions or surface interaction-facilitated dissociation phenomena. During liver or renal disease and acute-phase conditions plasma protein binding of drugs may be affected. Changes in the unbound drag fraction do not always result in proportional changes in clearance or distribution volume. Potential changes in the unbound concentration in steady-state as well as the fluctuations in total plasma levels depend on the extent of protein binding of a drug, the relative change in the unbound drug fraction, type of clearance, the size of the distribution volume, route of administration as well as concomitant changes in intrinsic (cellular) clearance function. Optimization of dosage regimens for certain drags and interpretation of liver function tests with diagnostic dyes may largely benefit from determination of the unbound rather than the total concentration of the drags involved.

Key words

Albumin Clearance, hepatic Drag transport Liver diseases Metabolism Orosomucoid Pharmacokinetics Protein binding 

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1987

Authors and Affiliations

  • Dirk K. F. Meijer
    • 1
  • Peter Van Der Sluijs
    • 1
  1. 1.Department of Pharmacology and Therapeutics, Faculty of PharmacyState University of GroningenAW GroningenThe Netherlands

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