Disposition and placental transfer of etidocaine in pregnancy

Summary Following epidural administration of etidocaine hydrochloride to non-pregnant and pregnant patients, a similar rate of absorption was observed and there was no significant difference in total systemic blood clearance (Cl_sb) of etidocaine in the two groups. There were no major differences in the urinary excretion of etidocaine and metabolites in 48 h urine in both groups. The ability of pregnant women to form the N-glucuronide of the metabolite ABX (2-amino-2-butyroxylidide) was similar to that of non-pregnant individuals. In vitro experiments showed that the blood/plasma concentration ratio () of etidocaine was significantly higher in pregnant females than in males, presumably due to the lower haematocrit in females. The fraction unbound in plasma (f_p) of etidocaine was low in control subjects (mean 0.057) and was not significantly different in pregnant women of 35 to 37 weeks gestation. A marked increase in f_p was observed in pregnant women during delivery (mean 0.264). This finding has potentially serious clinical implications because it is the unbound drug in blood which is pharmacologically important. Placental transfer of etidocaine was rapid and the cord/maternal venous blood concentration ratio at delivery (CM_b) was, with one exception, always less than unity (mean 0.342). Following epidural administration of etidocaine to pregnant women in labour, measurable concentrations of mono-dealkylated metabolites of etidocaine, PABX (2-N-propylamino-2-butyroxylidide) and EABX (2-N-ethylamino-2-butyroxylidide) were detectable in maternal blood within 5 min and cord blood within 30 min. The CM_b for PABX and EABX was 0.401 and 0.658 respectively.List of Abbreviations Used ABX 2-Amino-2-butyroxylidide - EABX 2-N-Ethylamino-2-butyroxylidide - PABX 2-N-Propylamino-2-butyroxylidide - Cl_sb Total systemic blood clearance - Cl_sp Total systemic plasma clearance - Blood/plasma concentration ratio - f_p Fraction of unbound drug in plasma - f_pw Fraction of free drug in plasma water in blood - C_mb Cord/maternal venous blood concentration ratio at delivery - C_mp Cord/maternal venous plasma concentration ratio at delivery - t_1/2 Terminal phase half-life - t_p Time of attainment of peak plasma concentration - E Mean hepatic extraction ratio - Q Liver blood flow