Abstract
Extract: The binding of diphenylhydantoin (DPH) to plasma proteins was studied with an equilibrium dialysis method in plasmas in which concentrations of free fatty acids (FFA) were varied by physiologic means. In blood-perfused dog subcutaneous adipose tissue, sympathetic nerve stimulation caused an increase in plasma FFA concentration from control values of 0.26–0.58 mM to peak levels of 0.63 to 3.44 mM. There was a linear relation between the binding of DPH and the FFA concentration in plasma from the same dog. When rat epididymal adipose tissue was incubated in dog plasma containing DPH, DPH protein binding decreased and tissue binding of the drug increased with increasing lipolytic rate. In plasma from 42 newborn infants the degree of DPH binding was significantly related to the albumin concentration as well as the bilirubin to albumin and FFA to albumin concentration ratios.
Speculation: Our data indicate that physiologically occurring variations in plasma FFA concentration can alter the plasma protein binding of drugs. We propose that such displacement will be quantitatively most important in blood perfusing adipose tissue during lipolysis and that the effect might lead to a preferential distribution of the drug to fat tissue during lipolysis.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fredholm, B., Rane, A. & Persson, B. Diphenylhydantoin Binding to Proteins in Plasma and Its Dependence on Free Fatty Acid and Bilirubin Concentration in Dogs and Newborn Infants. Pediatr Res 9, 26–30 (1975). https://doi.org/10.1203/00006450-197501000-00005
Issue Date:
DOI: https://doi.org/10.1203/00006450-197501000-00005
Keywords
This article is cited by
-
Pharmacokinetics of Antibacterial Agents in the CSF of Children and Adolescents
Pediatric Drugs (2013)
-
Considerations in the Rational Design and Conduct of Phase I/II Pediatric Clinical Trials: Avoiding the Problems and Pitfalls
Clinical Pharmacology & Therapeutics (2007)
-
Mechanisms of anticonvulsant drug action
European Journal of Pediatrics (1987)
-
Pharmakokinetische Bedeutung der Proteinbindung
Klinische Wochenschrift (1978)
-
Lack of relationship between serum free fatty acids and impaired plasma protein binding of diphenylhydantoin in chronic renal failure
European Journal of Clinical Pharmacology (1976)