Plasma protein binding of etidocaine during pregnancy and labour

Preliminary studies of the ultrafiltration method for measuring the extent of plasma protein binding of etidocaine showed that etidocaine binding was both pH and concentration dependent. Etidocaine (1 microgram/ml) was found to bind avidly to a physiological concentration (74 mg/dl) of alpha 1-acid glycoprotein (alpha 1-AGP) (7.23 +/- 0.64%, mean +/- SD, unbound). In vitro investigation of etidocaine binding in plasma obtained from blood bank donors and from 19 pregnant women prior to induction of labour, during early labour, mid-labour and delivery showed no difference in etidocaine binding (10.3 +/- 3.3%, 7.06 +/- 2.66%, 8.15 +/- 2.57%, 7.84 +/- 3.74% and 9.28 +/- 6.06% unbound respectively). There was a significant increase in the mean plasma total free fatty acid (FFA) concentration from pre-labour (0.535 +/- 0.240 mM) to delivery (0.948 +/- 0.28 mM), while plasma albumin and beta-lipoprotein concentrations remained constant. Alpha 1-Acid glycoprotein concentration tended to increase slightly from pre-labour to early labour (p less than 0.1) but was still within the normal physiological range. There was no correlation between etidocaine binding ratio and the concentrations of FFA or plasma proteins except for a poor correlation with the alpha 1-AGP concentration (r = 0.361, p less than 0.05). Storage of plasma and inadequate control of plasma pH during ultrafiltration appeared to give spurious binding values. These studies with the extensively bound basic drug etidocaine suggest that unlike many acidic drugs which are bound predominantly to serum albumin, the binding of alpha 1-AGP - bound basic drugs may be unaffected by pregnancy and labour.