Transfer of bupivacaine, lignocaine and pethidine across the rabbit placenta: influence of maternal protein binding and fetal flow.

The rabbit placenta perfused in itu was used to investigate the factors determining the placental transfer of drugs used in labour. Each doe was given an intravenous infusion of pethidine, lignocaine, bupivacaine and antipyrine concurrently, and the umbilical circulation was artificially perfused with Mammalian Krebs' bicarbonate buffer. The umbilical flow rate was varied between 0.25 and 4.0 ml/min. Drugs were analysed in maternal plasma and umbilical effluent by gas liquid chromatography . Maternal protein binding and lipid solubilities were also determined, and were high for bupivacaine, low for antipyrine and intermediate for pethidine and lignocaine. The Cuv /Cma (mean +/- s.e.) at 1.0 ml/min for antipyrine was 0.74 +/- 0.036; for pethidine, 0.64 +/- 0.04; for lignocaine, 0.5 +/- 0.026; and for bupivacaine 0.072 +/- 0.006. This is the same rank order as is observed for the drugs in humans. The placental clearance increased with flow rates up to 2.0 ml/min for antipyrine and up to 4.0 ml/min and probably more for pethidine, lignocaine and bupivacaine. Transfer rate is therefore reduced by maternal protein binding, is flow-dependent at low flows, and permeability-dependent at high flows for the less lipid-soluble compounds.