Optimization of Method for Measuring AGP-mediated Protein Binding in Dog Plasma

Poster Authors:

Janis Kuka, Luke Hanley, Coral Munday, Katherine Fenner

Pharmaron UK Ltd, Hertford Road Hoddesdon Hertfordshire, EN11 9FH, UK.

Understanding AGP Protein Binding and Its Impact on Dog Pharmacokinetics

It is well described that due to a polymorphism in the dog the expression of acid-1-glycoprotein (AGP) can be variable, meaning that for some drugs, the pharmacokinetics between dogs is variable. Here we share in-house work where plasma samples taken from a number of dogs have been characterized, using propranolol. Propranolol is a basic drug that pre-dominantly binds to AGP and indeed the determined unbound fraction in plasma (fu) correlates to the measured level of AGP in each plasma sample. The free fraction of unknown compounds can be determined in these characterized plasma samples and then correlated to the pre-determined levels of AGP. Additionally, a potential new methodology, comparing compound levels in dialyzed plasma and buffer to increase throughput was evaluated.