Serum protein binding of drugs during and after pregnancy in humans

Abstract

The serum protein binding of 3 weak acidic drugs (salicylic acid, sulfisoxazole and phenytoin), 1 weak base (diazepam) and 1 steroid (dexamethasone) was determined in pregnant women at 7 time periods during pregnancy and at 2 time periods post partum and in a group of nonpregnant women of childbearing age. The serum free fraction values (ratio of concentrations, free to total drug) of all drugs rose during pregnancy, primarily after 15 wk of gestation and remainded elevated for at least 1-5 days post partum. Pregnancy had the greatest effect on protein binding of sulfisoxazole, diazepam and salicylic acid. The magnitude of this effect is such that quantitatively significant changes in the pharmacokinetic and pharmacodynamic characteristics of certain drugs may be expected to occur during pregnancy (in addition to possible changes caused by other pregnancy-related effects, i.e., altered activity of drug-metabolizing enzyme systems). All drugs but dexamethasone exhibited significant negative correlations between free fraction values and serum albumin concentrations during pregnancy. The serum protein binding of salicylic acid, but not the other drugs tested, was more extensive in nonpregnant women who were not taking oral contraceptives than in those who were.