Fm. Belpaire et al., PROTEIN-BINDING OF PROPRANOLOL AND VERAPAMIL ENANTIOMERS IN MATERNAL AND FETAL SERUM, British journal of clinical pharmacology, 39(2), 1995, pp. 190-193
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.