Free Webinar
Neglecting AAG Binding can Lead to
Overestimation of Drug Efficacy
About the Webinar
Alpha-1-Acid-Glycoprotein can have a strong effect on a drug's pharmacokinetics and pharmacodynamics. COVID-19 research has drawn attention to this often-neglected fact that the acute phase protein AAG’s concentration varies strongly with physiological and disease condition. This causes a substantial reduction in free fraction when the compounds bind strongly to AAG, which in turn reduces efficacy.
The webinar summarizes the latest research, illustrates the problem using PK/PD simulations, and shows how AAG binding can be measured early on to avoid pitfalls.
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Problem: Summary of latest research findings
AAG concentration increases with COVID-19 infections and many other ailments such inflammatory diseases and cancer. Diseases trigger AAG levels to increase 50%, 3-fold, or even 1000-fold. But also, pregnancy and physiological state changes can significantly affect AAG concentrations and thus drug availability.
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Analysis: PK/PD simulations show when AAG binding can affect fu
Simulations with Simcyp and other tools show that the critical effects of AAG arise when drugs bind weakly to albumin and much stronger to AAG. Thus, having a reliable screening tool for measuring binding to the two main plasma binding proteins can prevent unexpected trial outcomes.
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Solution: Screening methods for AAG Binding
The most accurate way to assess liabilities of AAG binding is measuring individual dissociation constants between drug and AAG as well as albumin. The Transil AGP Binding Kit as well as the Transil HSA Binding Kit are an effective way to solve this problem.
Dr. Hinnerk Boriss
Webinar Host