Binding of drugs to cord plasma

Abstract

The purpose of the present work is to compare the binding of several drugs—diphenylhydantoin (DPH), cephalothin (CPT), cephaloglycin (CPG), imipramine (IMI), and diazoxide (DX) to plasma from adults and from newborns. Adult plasma was collected from 3 healthy subjects and cord plasma from 9 term newborns. The drugs, except for DX, were 14C labeled. After equilibrium dialysis with the plasma sample, the % binding of drug to plasma was determined. In this series, the average albumin in the adult plasma is 4.1 and in cord plasma 3.4 gm%. For each of the drugs studied, the binding to adult plasma is greater than to cord plasma. The average value for binding of DPH to cord plasma is 74% compared to 83% bound in adult samples. Using CPT, 72% of the drug is bound in cord plasma and 80% in adult plasma. CPG is not highly bound and the difference is not striking (60% to cord plasma and 63% to adult plasma). The binding of IMI to adult plasma is 89% and to cord plasma is 74%, but this drug is bound to plasma proteins other than albumin since binding to 3% human albumin is only 61%. DX is a very hightly bound drug in both cord plasma (88%) and adult plasma (92%). The differences in binding between adult and newborn plasma can be correlated most clearly with reduced albumin concentration in the newborn. If adult plasma is diluted to the albumin concentration of cord plasma, the binding data are similar to that for cord plasma. The infant, with normally lower plasma albumin levels, will therefore have a greater fraction of free drug in plasma which is available for tissue distribution and for glomerular filtration.