Protein binding of propranolol and verapamil enantiomers in maternal and foetal serum.

Abstract

The protein binding of the enantiomers of propranolol and verapamil was measured in 19 pairs of maternal and foetal serum obtained at delivery. The binding of the enantiomers of both drugs was lower in foetal than in maternal serum. In maternal serum the mean (± s.d.) unbound percentages 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 serum the values were 38.8 ± 8.6 and 40.4 ± 10.6 for R-and S-propranolol, 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 between 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 ± 0.072) than in the foetus (0.973 ± 0.068). For verapamil, the difference 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 a1-acid glycoprotein (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 < 0.001) with the AAG concentration (r propranolol: R 0.749, S 0.746; r verapamil: R 0.753, S 0.782). Our findings show that measurement of concentrations of total, unresolved drug allow a reasonably accurate assessment of transplacental gradients of individual isomers.

Transplacental Pharmacokinetic Model of Digoxin Based on Ex Vivo Human Placental Perfusion Study

“…K i,MDR1,MVM,VRP overlapped with the blue line. The simulations by the developed transplacental PK model of digoxin followed Holcberg's ex vivo studies except for enhanced maternal digoxin concentrations in the case of co-administration with inhibitor (Pedersen et al, 1983;Rodin et al, 1988) and f u,med in human plasma (Hubert et al, 1985;Mihaly et al, 1987;Belpaire et al, 1995;Hebert et al, 2008) (Supplemental Table 5).…”