Format

Send to

Choose Destination
J Pharm Sci. 2012 Mar;101(3):1327-35. doi: 10.1002/jps.23013. Epub 2011 Dec 9.

Impact of recovery on fraction unbound using equilibrium dialysis.

Author information

1
Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Road, Groton, Connecticut 06340, USA. li.di@pfizer.com

Abstract

Historically, recovery had been used to evaluate the data quality of plasma protein binding or tissue binding obtained from equilibrium dialysis assays. Low recovery was often indicative of high nonspecific binding, instability, or low solubility. This study showed that, when equilibrium was fully established in the dialysis assay, low recovery due to nonspecific binding had no impact on the determination of fraction unbound. The conclusion was supported by the principles of the equilibrium dialysis assay, experimental data, and mathematic simulations. The results suggested that the use of recovery as an acceptance criterion for the equilibrium dialysis assay in drug discovery was too restrictive, and introduced the additional burden of repeating studies unnecessarily.

PMID:
22161810
DOI:
10.1002/jps.23013
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center