Disposition of bupivacaine and its metabolites in the maternal, placental,and metal compartments in rats

Background: This study was designed to determine the disposition of bupivac aine and its metabolites in the maternal, placental, and fetal compartments , using multiple sampling time points in chronically prepared awake pregnan t rats. Methods: All animals received an intravenous infusion of bupivacaine at a r ate of 0.33 mg . kg(-1) . min(-1) over a period of 15 min. The fetuses were delivered either at the end of infusion or at 2 or 4 h after dosing. Mater nal and fetal blood and tissue samples were obtained for the assays of bupi vacaine and its metabolites using capillary gas chromatography-mass spectro metry. Results: The elimination half-life of bupivacaine was 37.7 min. The major m etabolite was 3'-hydroxybupivacaine. Bupivacaine and 3'-hydroxybupivacaine were present in all samples at the end of administration. The fetal to mate rnal concentration ratio of bupivacaine in plasma was 0.29, and in the plac enta was 0.63. The amnion contained the highest bupivacaine concentration: threefold higher in the maternal and 11-fold higher than in the fetal plasm a. At 4 h after dosing, bupivacaine was no longer detectable in any materna l and fetal samples, whereas 3'-hydroxybupivacaine was still present in all tissues except the fetal plasma and heart. Conclusions: These data Indicate that a considerable amount of bupivacaine is taken up by both sides of the placenta, as well as the amnion and myomet rium. 3'-Hydroxybupivacaine was present in all tissues except the fetal pla sma and heart samples, even after the parent compound became no longer dete ctable. Whether this slow elimination of 3'-hydroxybupivacaine causes any a dverse effects on the fetus-newborn needs to be explored.