ISSN:
1573-739X
Keywords:
Albumin
;
Clearance, hepatic
;
Drag transport
;
Liver diseases
;
Metabolism
;
Orosomucoid
;
Pharmacokinetics
;
Protein binding
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The liver is a major site for synthesis and catabolism of plasma proteins. Albumin has various binding sites for anionic drugs,α 1acid 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01960738
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