PROTEIN-BINDING OF PROPRANOLOL AND VERAPAMIL ENANTIOMERS IN MATERNAL AND FETAL SERUM

The protein binding of the enantiomers of propranolol and verapamil wa s measured in 19 pairs of maternal and foetal serum obtained at delive ry. The binding of the enantiomers of both drugs was lower in foetal t han in maternal serum. In maternal serum the mean (+/- s.d.) unbound p ercentages were 22.4 +/- 6.2 and 20.7 +/- 6.6 for Rand S-propranolol, and 16.8 +/- 5.5 and 22.5 +/- 6.2 for R- and S-verapamil; in foetal se rum the values were 38.8 +/- 8.6 and 40.4 +/- 10.6 for R- and S-propra nolol, and 34.7 +/- 10.5 and 44.8 +/- 10.7 for R- and S-verapamil. For propranolol, in maternal, but not in foetal serum, the difference bet ween the binding of the R- and S-enantiomers was significant; the R/S ratio was significantly (P < 0.01) larger in the mother (1.099 +/- 0.0 72) than in the foetus (0.973 +/- 0.068). For verapamil, the differenc e in binding between the R- and S-enantiomers was significant in both maternal and foetal serum, but the R/S ratio was similar in mother (0. 735 +/- 0.098) and foetus (0.763 +/- 0.070). Serum al-acid glycoprotei n (AAG) concentrations were markedly higher and albumin concentrations slightly lower in maternal than in foetal samples. The binding of the four enantiomers in maternal and foetal serum was correlated (P < 0.0 01) with the AAG concentration (r propranolol: R 0.749, S 0.746; r ver apamil: R 0.753, S 0.782). Our findings show that measurement of conce ntrations of total, unresolved drug allow a reasonably accurate assess ment of transplacental gradients of individual isomers.