Addressing the Accuracy of Plasma Protein Binding Measurement for Highly Bound Compounds Using the Dilution Method

In this study, the dilution method was evaluated, and the results showed that it gave similarfu values as those determined using the pre-saturation method without plasma dilution. The dilution method enables generation of accuratefu values and alignment with the regulatory recommendation of reportablefu values of  ≥ 0.01 for DDI prediction. We recommend using the dilution method to bridge the regulatory recommendedfu limit of 0.01 for DDI prediction and the pre-saturation or equivalent methods for definitive plasma protein binding studies. As the pharmaceutical industry continues to generate high quality PPB data, regulatory agencies will gain confidence in the accuracy offu measurements for highly bound compounds, and thefu lower limit may no longer be needed in the future.Graphical Abstract
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research