PMID: 8946671Dec 1, 1996Paper

Plasma protein binding of phenylacetate and phenylbutyrate, two novel antineoplastic agents

Therapeutic Drug Monitoring
S BoudoulasW D Figg

Abstract

Phenylacetate and phenylbutyrate, two novel inducers of tumor cytostasis and differentiation, are currently in clinical trials for the treatment of cancer in adults. The purpose of our study was to evaluate the plasma protein-binding characteristics of phenylacetate and phenylbutyrate in the plasma of normal volunteers and that of patients with cancer. Drug plasma protein-binding analysis was examined using three separate devices: a micropartition system and two equilibrium dialysis systems, all of which exhibited similar results. Phenylacetate and phenylbutyrate concentrations were determined by high-performance liquid chromatography. Both drugs exhibited concentration-dependent binding. Our results showed sodium phenylacetate to have a higher free fraction than sodium phenylbutyrate at corresponding concentrations (> 0.442 +/- 0.008 and > 0.188 +/- 0.001, respectively). Plasma pH did not greatly affect protein binding of either drug. As albumin concentration decreased, an increase in free fraction of both drugs was observed, however alpha 1-acid glyco-protein showed no change in free fraction as its concentration increased. Patients with cancer with lower levels of albumin showed an increase in free fraction with both phenyla...Continue Reading

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Citations

Aug 25, 2001·Cancer Letters·O WittA Pekrun
Dec 12, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Gerald CohenWalter H Hörl
Oct 16, 2015·Bulletin of Experimental Biology and Medicine·N P FadeevYu I Pustovalov
Jul 23, 1999·Biomedical Chromatography : BMC·Z LiuY Huang
Feb 12, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiao-Nan LiChing C Lau

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