Meperidine binding in maternal and fetal plasma

Abstract

Meperidine protein binding was measured in 9 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 .alpha.1-acid glycoprotein (.alpha.1-AGP) concentrations were higher (P < 0.01) in maternal than in fetal samples and there was a correlation between meperidine B/F and plasma .alpha.1-AGP concentration for the maternal and fetal samples (r = 0.752, P < 0.01). Binding studies with purified .alpha.1-AGP showed that this was a cause-effect relationship. The transplacental binding differential was attributable partially to the maternal-fetal difference of plasma .alpha.1-AGP concentrations. Meperidine was 17.5 .+-. 0.35% bound in a 3.5 gm/100 ml solution of human serum albumin but there was an inverse correlation (r = -0.798, P < 0.01) between B/F 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 .alpha.1-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.