Meperidine binding in maternal and fetal plasma

Meperidine protein binding was measured in nine pairs of maternal and fetal plasma samples obtained at delivery. For the maternal samples, percent bound and binding ratio (bound/free, B/F) were 63.3 ± 6.18% (SD) and 1.79 ± 0.45, and for the fetal samples the corresponding values were 51.7 ± 4.53% and 1.09 ± 0.21. In each case the binding was higher in the mother than in the fetus (p < 0.01). Plasma α₁-acid glycoprotein (α₁-AGP) concentrations were higher (p < 0.01) in maternal than in fetal samples, and there was a correlation between meperidine BIF and plasma α₁-AGP concentration for the maternal and fetal samples (r = 0.752, p < 0.01). Binding studies with purified α₁-AGP showed that this was a cause-effect relationship. The transplacental binding differential was attributable partially to the maternal fetal difference of plasma α₁-AGP concentrations. Meperidine was 17.5 ± 0.35% bound in a 3.5 gm/100 ml solution of human serum albumin; however, there was an inverse correlation (r = -0.798, p < 0.01) between BIF and plasma albumin concentration for the maternal and fetal samples. A relatively large proportion (75%) of the overall variability in B/F was accounted for by plasma α₁-AGP and albumin. Plasma binding of this basic drug was not greatly influenced by the perinatal levels of bilirubin and nonesterified fatty acids. The common clinical observation of greater fetal than maternal plasma total meperidine concentrations at delivery is not the result of more extensive protein binding in fetal than in maternal plasma.