Cross-species differential plasma protein binding of Propoxazepam, a novel analgesic agent.

Abstract

The purpose of this study was to characterize the Propoxazepam properties of bin ding to the human, dog and rat plasma proteins and to evaluate potential interspecies diffe rences in binding affinity. Methods. The stu dies on Plasma protein binding were conduc ted using the Rapid Equilibrium Dialysis system with subsequent LC MS/MS analysis. The albumin binding of the substances was cha racterized by the percentage of bound drug. Results. Propoxazepam was highly bound to the plasma proteins in rats, dogs and humans. The extent of Propoxazepam binding in human plasma was similar to that observed in rat plasma whereas it was slightly lower in dog plasma, following dialysis for 8 hours. Conclusions. No concentration dependent effects on plasma protein binding were observed in the species investigated for Propoxazepam. Overall mean free fractions of Propoxazepam were 1.60 %, 2.90 % and 1.96 % in rats, dogs and humans, respectively. The results obtained in this work gave insights on the role of HSA in distributing Propoxazepam to target tissues and in determining their pharmacological properties. The results are crucial for the development of Benzodizepines-based therapeutics drugs.