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Thread: Protein binding and the serum concentration of a medication

  1. #1

    Default Protein binding and the serum concentration of a medication

    The fraction of drug that is unbound (fu) dose not vary with the drug concentration for most drugs that are bound primarily to albumin. This is because the number of protein binding sites far exceeds the number of drug molecules available for binding. When the plasma concentrations for drugs bound to albumin exceed 25 to 50 mg/L, however, albumin binding sites can start to become saturated. As a result, fu will change with the plasma drug concentration. For those drugs that do not reach serum concentrations capable of saturating protein binding sites, the plasma protein concentration and the binding affinity of the drug for the protein are two major factors that control the fraction unbound (flu).

    Low Plasma Protein Concentrations

    Low plasma protein concentrations decrease the plasma concentration of bound drug (C bound); however, the concentration of free drug (C free) generally is unaffected, since the free drug that is released into plasma secondary to low plasma protein concentrations equilibrates with the tissue compartment and/or cleared from the body. Therefore, if the volume of distribution (V) is relatively large, only a minor increase in C free will result.

    The relationship between the plasma drug concentration and the plasma protein concentration can be expressed as follows:

    Protein binding and the serum concentration of  a medication-protein-binding-png

    C' represents the patient's plasma drug concentration, P' represents the patient's plasma protein concentration. CNormal Binding is the plasma drug concentration that would be expected if the patient's plasma protein concentration were normal (PNL), fu is the free fraction associated with "normal plasma protein binding".

    The equation above could be written as follows:

    Protein binding and the serum concentration of  a medication-protein-binding2-png

    Binding Affinity

    The binding affinity of plasma protein for a drug can alter the faction of drug which is free (fu), e.g., patients with uremia have less affinity for phenytoin compared with non-uremic individuals. In such case, the protein concentraion is normal, the decreased binding affinity of the drug for protein has decreased the reported drug concentration (total drug concentration). The concentration of free, or active, drug remains the same because drug that is nonspecific binding sites is taken up by nonspecific binding sites in the tissue and/or cleared from the body.

    As a result, fu increases. The concentration of free drug in uremic patients is comparable to that in non-uremic patients, despite lower total serum concentrations of the drug.

    In summary, any factor that alters protein binding becomes clinicallly important when a drug is highly protein bound (i.e., if fu is <0.1 or 10% unbound).
    Last edited by CheneyHsiung; Thu 8th August '13 at 1:37am.

  2. #2
    Pre-pharmD Year 1
    Join Date
    Aug 2013


    The fact of drug binding to low plasma does not influence the concentration of unbound drug in plasma at steady state but does influence the interpretation of total drug concentrations. An increase in free fraction (reduction in the extent of binding) decreases the therapeutic & poisonous ranges for total drug concentrations.

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