Diphenylhydantoin Binding to Proteins in Plasma and Its Dependence on Free Fatty Acid and Bilirubin Concentration in Dogs and Newborn Infants
作者:
BERTIL FREDHOLM,
ANDERS RANE,
BENGT PERSSON,
期刊:
Pediatric Research
(OVID Available online 1975)
卷期:
Volume 9,
issue 1
页码: 26-30
ISSN:0031-3998
年代: 1975
出版商: OVID
数据来源: OVID
摘要:
ExtractThe 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.SpeculationOur 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.
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