Drugs protein binding and clinical practice
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1
University of Athens, Department of Pharmacology, Greece
Binding of drugs to various sites (receptors, carrier proteins, enzymes) is an important parameter critically determining their pharmacokinetic and pharmacodynamic properties.
Drug transport and disposition in the organism are variable, depending on non-specific and reversible binding to plasma and tissue proteins (such silent carrier). Albumin possesses the key specific sites for acidic (1) and basic (2) drug binding and can interact with them in plasma. Additionally, a1-acid glycoprotein and lipoproteins contribute significantly to this process
The amount of proteins capable to bind drugs represents a silent drug depot for free drug concentration.
Active is only the unbound drug fraction that is responsible for the pharmacological effect.
The extent of drug binding to proteins is influenced by factors related to albumin, by the presence of endogenous substances such hormones and metabolic products, by the pH and the temperature, by the co-administration of other drugs and by any underlying diseases, that can modify protein stereochemistry, and body physiology and biochemistry be responsible molecules release interacting with drugs for their binding site.
Displacement of drugs from plasma or tissue binding sites by another drug or by endogenous substances lead to increase in the unbound drug concentration and its pharmacodynamic effect.
In clinical practice however the extent of protein binding may have only a limited relevant effect because the changes in protein binding are usually very limited in vivo to cause significant alterations in unbound drug concentrations. For low clearance drugs with a low therapeutic index and a small Vd , the temporary increase in drug concentration and the increased variation within a dosing interval may be clinically relevant e.g warfarin.
The consequences, following the displacement from plasma or tissue binding sites of one drug by another, depend on the distribution and elimination profile of each drug and need monitoring evaluation.
Keywords:
drug protein binding,
Drug Transport
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Invited speaker
Topic:
Food, drugs and environmental xenobiotics
Citation:
Tesseromatis
C
(2010). Drugs protein binding and clinical practice.
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00204
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Received:
05 Mar 2011;
Published Online:
04 Nov 2010.
*
Correspondence:
Dr. Christine Tesseromatis, University of Athens, Department of Pharmacology, Athens, Greece, ctesser@med.uoa.gr