Plasma proteins implication

Weiss, M., Fresenau, M., Monius, T., Stutz, A., Billich, A. (2008). Binding of pimecrolhnus and tacrolimus to skin and plasma proteins implications for systemic exposure after topical application. Drug Metab. Dispos. June 4, 2008. (Epub ahead of print), DOI 10.1124/dmd.l08.021915. 

B21. Brodie, B. B., Pharmacological and clinical implications of drug transport. In Tr sport Function of Plasma Proteins (P. Desgrez and P. M. De Traverse, eds.), pp. 137-145. Elsevier, Amsterdam, 1966. 

Christensen, H., Baker, M., Tucker, G.T. and Rostami-Hodjegan, A. (2006) Prediction of plasma protein binding displacement and its implications for quantitative assessment of metabolic drug-drug interactions from in vitro data. Journal of Pharmaceutical Sciences, 95, 2778-2787. 

J.J.H.M. Lohman, in Plasma Protein Binding of Drugs, Implications for Therapeutic Drug Monitoring, Thesis, Leiden, The Nerherlands (1986). 

The binding of foreign compounds to plasma proteins has several important implications. 

Unlike most plasma proteins and red blood cells, the metabolism and disposition of plasma lipoproteins is highly regulated and mediated in part by specific receptors located at discreet sites around the body. The concentrations of plasma lipoproteins in the blood can also vary significantly (up to tenfold) as a function of diet, disease, and both within and between healthy individuals. The implications, therefore, for the clearance of drug molecules associated with these plasma lipoproteins are considerable but have not been clearly defined. 

S. Toon and W, F, Trager, "Pharmacokinetic implications of stereoselective changes in plasma-protein binding Warfarin-sulfinpyrazone," /. Pharm. ScL, 73 1671-1673 (1984). 

Tozer, T.N. Implications of altered plasma protein binding in disease states. In Pharmacokinetic Basis for Drug Treatment, Benet, L.Z., Massoud, N., Gambertogho, J.G., Eds. Raven Press New York, 1984 173-193. 

Because many immune factors are implicated in the pathogenesis of glomerulonephritis, plasmapheresis may be used to remove these mediators. During the procedure, whole blood is removed from the body and centrifugation is used to separate the cellular elements from the plasma. The cells are then infused back to the patient after resuspension in saline or plasma substitute. The plasma proteins, presumably including the pathogenic immune factors, are thereby removed from the patient. 

Many disease states can cause individual variation in response to drugs. Any disease that results in alteration in the pharmacokinetics of a drug will create these variations. Diseases of the liver and kidney, any disease that affects intestinal motility, mal-absorption syndromes and any condition that reduces plasma protein concentration are all implicated. Some diseases can alter the physiological sensitivity to a drug at its site of action. 

Many drugs also bind to albumin, which may have important pharmacologic implications. For example, when a drug binds to albumin, such binding will likely lower the effective concentration of that drug and may lengthen its lifetime in the circulation. Drug dosimetry may need to be recalculated if a patient s plasma protein concentration is abnormal. 

Valproic acid In addition to competing for phenytoin plasma protein binding sites, valproic acid inhibits the metabolism of phenytoin, phenobarbital, and lamotrigine. Hepatic biotransformation of valproic acid leads to formation of a toxic metabolite that has been implicated in the hepatotoxicity of the drug. 

The possible adsorption of low molecular weight components from sheep plasma onto surfaces carries with it the implication of some possible interaction of these components with plasma proteins or the surface itself, which might be as significant as the proteins themselves in determining the thrombogenicity of the surface. 

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