Biopolym. Cell. 2021; 37(6):459-468.
Biomedicine
Cross-species differential plasma protein binding of Propoxazepam, a novel analgesic agent.
1Golovenko M. Ya., 2Reder A. S., 1Larionov V. B., 1Andronati S. A., 3Akisheva A. S.
  1. O. V. Bogatsky's Physico-chemical Institute, NAS of Ukraine
    86, Lustdorfskaya dor., Odessa, Ukraine, 65080
  2. SLC «INTERCHEM»
    86, Lustdorfskaya dor., Odessa, Ukraine, 65080
  3. Odessa I. I. Mechnikov National University
    Dvoryanskaya Str., 2, Odessa, Ukraine, 65082

Abstract

Aim. To characterize the Propoxazepam properties of bin-ding to the human, dog and rat plasma proteins and to evaluate potential interspecies differences in binding affinity. Methods. The studies on Plasma protein binding were conducted using the Rapid Equilibrium Dialysis system with subsequent LC MS/MS analysis. The albumin binding of the substances was characterized 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.
Keywords: Propoxazepam, plasma protein, interspecies binding

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