Plasma Protein Binding

Plasma Protein Binding

Plasma protein binding (PPB) affects the time that a drug stays in the body and can also have an effect upon the drug's efficiency.

Why is Plasma Protein Binding Important?
If the majority of the drug is bound to plasma protein then only the unbound fraction can have a biological effect or be metabolised/excreted. Therefore, the degree of binding to plasma proteins significantly influences the pharmacokinetic and pharmacodynamic properties of a drug. The efficacy of the drug will be related to the exposure to the amount of unbound drug in plasma, i.e. the proportion free to penetrate into surrounding tissues. The bound drug in plasma can also serve as a reservoir for free drug removed by various elimination processes thus prolonging the duration of action. The proportion of binding can also be affected if two drugs are used at the same time because each drug may displace a proportion of the other from being bound to the plasma protein, resulting in a greater proportion of unbound drug. The bulk of experimental data available relates to percent or fraction of drug bound to all plasma proteins (mainly serum albumin and a1-acid glycoprotein).

PPB Model
Asteris provides a classification model indicating whether a drug will be more than 90% bound.  The model was built using a data set of 1107 compounds, somewhat biased toward high percentage values with 33% of the compounds reported as >= 90% bound. Values of % bound < 90% were classified as low, values >= 90% were classified as high. The structures were assigned randomly to training (n = 775), internal evaluation (n = 166) and independent test (n = 166) sets. The latter was excluded from the model development process. The model is a random forest that predicts the extent of test set compounds' plasma protein binding as either 'high' or 'low' in relation to the threshold described above. For the internal evaluation set, used to monitor the performance of the model during training, predictions of high and low plasma protein binding were correct on 81% and 87% of occasions respectively. The corresponding figures for the independent test set were also 81% and 87%.

Observed vs Predicted PPB90 Category