PLASMA-PROTEIN BINDING OF DISOPYRAMIDE IN PREGNANT AND POSTPARTUM WOMEN, AND IN NEONATES AND THEIR MOTHERS

1. The protein binding of disopyramide was measured in plasma obtained from nonpregnant women, pregnant women in the first, second, and third trimesters, matched pairs of mothers and neonates (cord plasma), and 1 month postpartum women (n = 6 or 8 of each). 2. Plasma samples spiked with 0.2‐12.0 micrograms ml‐1 of the drug were ultrafiltered and the free fractions were measured with a fluorescent polarization immunoassay. 3. The mean (+/− s.d.) percentages of free drug at a total concentration of 3.0 micrograms ml‐1 observed in the third trimester (46 +/− 9%) and neonate (79 +/− 5%) groups were greater (P less than 0.05 or 0.01) than that in the non‐pregnant group (34 +/− 7%). In contrast, the corresponding value observed in the postpartum group (23 +/− 8%) was less (P less than 0.05) than that in the non‐pregnant group. In addition, there was a significant (P less than 0.01) difference in the mean percentage of free drug at 3.0 micrograms ml‐1 in plasma from mothers (43 +/− 9%) and neonates (79 +/− 5%). 4. A multiple regression analysis indicated that alpha 1‐acid glycoprotein (r = ‐0.88, P less than 0.01), rather than albumin (r = ‐0.008), dominated the binding of disopyramide within the therapeutic range of drug concentration. An analysis of the binding parameters of disopyramide suggested that alterations in binding were attributable to changes in the capacity rather than the affinity of binding.(ABSTRACT TRUNCATED AT 250 WORDS) 1990 The British Pharmacological Society