Significance and method of determination of plasma protein binding rate

The plasma protein binding rate refers to the percentage of the therapeutic dose of the drug bound to the plasma protein after most of the drug is absorbed into the blood and bound to the plasma protein. The higher the plasma protein binding rate, means that the drug can be fully transported in the blood, can be released continuously in the blood, the drug concentration is relatively stable and can exert a better therapeutic effect. The plasma protein binding rate is low and the drug metabolism is faster. , the concentration is unstable, which will affect the therapeutic effect. In patients with hypoalbuminemia, due to the decrease in albumin concentration, the binding rate of plasma protein decreases, which often affects the therapeutic effect.

Under normal circumstances, various drugs are bound to plasma proteins at a certain ratio, and there are often both bound and free forms in the plasma, and only free-form drugs have drug activity. When the two drugs are used in combination, the drug molecule with stronger protein binding ability occupies the binding site, so that other drugs cannot be fully combined, so that the free part of the latter increases and the drug effect is enhanced. This interaction is meaningful for some drugs with high protein binding rates, so we should pay attention to those drugs with strong drug effect or high toxicity, so as to prevent the drug from changing from the position of the binding part and enhance the drug effect, which often has a certain risk sex. The plasma protein binding rate is reversible loose binding, the molecular weight of the bound drug increases, it cannot be transmembrane transported, metabolized, and excreted, and temporarily loses its pharmacological activity, and some drugs can undergo competitive exclusion on the plasma protein binding site.

The plasma protein binding capacity of the drug is affected by the drug concentration, the quality and quantity of the plasma protein, and the dissociation constant. The drug is different and the binding rate decreases with the increase in the dose. The plasma protein binding rate of drugs recorded in pharmacology books is the value measured in normal people within the usual dose range.

Competitive displacement occurs when two drugs are used in combination. If the binding rate of a certain drug reaches 99%, and when it is replaced by another drug and decreases by 1%, the concentration of the free (pharmacologically active) drug will theoretically increase by 100%, which may lead to poisoning. However, during the replacement process of generic drugs, the free drug will be eliminated at an accelerated rate, and the concentration of free drug in plasma is difficult to increase continuously. Drugs may also compete with endogenous metabolites for binding to plasma proteins. For example, sulfa drugs displace bilirubin from binding to plasma proteins, which may cause kernicterus in newborns. When the plasma protein is too little (such as liver cirrhosis) or deteriorates (such as uremia), the drug plasma protein binding rate decreases and toxic reactions are prone to occur. Due to the limited plasma protein, when the drug with a high binding rate reaches saturation at the binding site, if the dose continues to increase, the concentration of the free drug in the plasma will increase greatly, causing toxic reactions.

The plasma protein binding rate can be determined by methods such as equilibrium dialysis, microdialysis, ultrafiltration, and ultracentrifugation. AxisPharm Labs is well equipped with all the necessary tools and instruments to perform in vitro ADME tests.

AxisPharm is a San Diego based bioanalytical LC/MS/MS service provider with more than 25 years experience in the field. Our bioanalytical chemistry department specializes in developing and validating robust bioanalytical methods for PK/TK sample analysis of small molecules, proteins, peptides, and metabolites using LCMS/MS (HPLC, UPLC, on-line SPE), HPLC/UV, and HPLC/FL. We have experience analyzing API and metabolites in various biological matrices and can provide bioanalytical support throughout all the stages of drug development.

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This release was published on openPR.