Cefazolin plasma protein binding saturability during pregnancy

Abstract

This article aims to document cefazolin (CFZ) plasma binding and its covariates during pregnancy and compare these observations with previously reported observations in nonpregnant adults. Maternal CFZ plasma samples were collected during in utero surgery. The unbound CFZ fraction was reported by median and range. Correlation (Spearman) and multiple regression were used to identify covariates (total CFZ concentration, albuminemia, gestational age) of the unbound CFZ fraction. Observations during pregnancy were compared with observations in nonpregnant adults (unpaired t test, multiple regression). Plasma (N = 130) samples were collected during 30 interventions. The median unbound CFZ fraction was 0.25 (range 0.14-0.41). Correlations between the unbound CFZ fraction and total CFZ plasma concentration (0.46), time after administration (-0.38), albuminemia (-0.39) and gestational age (-0.19) were statistically significant. The median unbound CFZ fraction was higher during pregnancy when compared to observations in nonpregnant adults (0.25 vs. 0.19, P < 0.001). In a multiple-regression model, total plasma CFZ concentration and albuminemia were covariates of the unbound CFZ fraction (r(2) = 0.4). The concept of saturability of CFZ plasma protein binding has been confirmed during pregnancy, but the free CFZ fraction is higher, likely explained by the lower albuminemia during pregnancy.