Protein binding of propranolol and verapamil enantiomers in maternal and foetal serum.
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 R- and 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 alpha 1-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.
Belpaire
F M
FM
Heymans Institute of Pharmacology, University of Gent Medical School, Belgium.
Wynant
P
P
Van Trappen
P
P
Dhont
M
M
Verstraete
A
A
Bogaert
M G
MG
D000328:Adult; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D009961:Orosomucoid / Q000378:metabolism*; D011247:Pregnancy / Q000097:blood*; D011433:Propranolol / Q000097:blood*; D011485:Protein Binding / Q000502:physiology; D012709:Serum Albumin / Q000378:metabolism; D013237:Stereoisomerism; D014700:Verapamil / Q000097:blood*
D009961:Orosomucoid; D012709:Serum Albumin; D011433:Propranolol; D014700:Verapamil