ELIMINATION OF BUPIVACAINE AND PETHIDINE FROM THE RABBIT FETOPLACENTAL UNIT

Bupivacaine 12.5 mg and pethidine 12.5 mg were administered as an i.v. infusion over 80 min in 15 near-term pregnant New Zealand white rabbits. After the infusion, pups were removed via individual hysterotomies every 30 min. Bupivacaine and pethidine were measured by gas chromatography in amniotic fluid, placenta, fetal plasma, fetal brain and maternal plasma, sampled as each fetal sac was opened. Pethidine was cleared from all compartments more rapidly than bupivacaine and for both drugs elimination rates were maternal plasma > placenta > amniotic fluid > fetal brain > fetal plasma. Concentrations of both drugs in fetal plasma correlated significantly only with those in fetal brain and not with those in maternal plasma, placenta or amniotic fluid, while there were positive correlations between the last three compartments. Nested analysis of covariance showed that only maternal plasma and placental concentrations of the two drugs decreased significantly with time. Maternal plasma half-lives for pethidine and bupivacaine were 1.0 and 2.0 h, and placental half-lives 1.9 and 2.5 h, respectively. The apparent fetal plasma half-life of pethidine was 9.9 h while there was apparently no net elimination of bupivacaine from fetal plasma.