Placental transfer of bupivacaine, pethidine and lignocaine in the rabbit. Effect of umbilical flow rate and protein content

Summary. The factors determining the placental transfer of drugs used in labour were studied in the rabbit placenta perfused in situ with Krebs bicarbonate buffer. During concurrent maternal intravenous infusion of bupivacaine, lignocaine, pethidine and antipyrine, drug concentrations were measured in maternal arterial plasma and placental effluent perfusate, the flow rate and protein content of which were varied. Protein binding and content were also measured. Placental clearance of antipyrine, which is unbound, was unaltered by perfusate protein content, and increased with umbilical perfusate flow up to 2 ml/min. Clearance of lignocaine and pethidine, which were 20–30% protein bound, increased to a small extent with perfusate protein, and were flow-dependent up to the maximum perfusate flow of 4 ml/min. Clearances of bupivacaine, which was > 80% bound, increased markedly with perfusate protein but, though flow-dependent, was one-tenth to one-fifth that of the other drugs. Fetal binding and glycoprotein content were less than maternal, hence the equilibrium fetal: maternal ratio is predictably lower for the highly bound bupivacaine than for lignocaine or pethidine. Measured fetal: maternal ratios of bupivacaine were, however, only one-half to one-third of the predicted equilibrium values, suggesting that bupivacaine does not unbind readily in a single transit through the rabbit placenta. Thus, though bupivacaine crosses the placenta more slowly than thc other drugs, the fetal dose of all these drugs will be greatest in healthy babies with good placental blood flows and high plasma proteins.