THE TRANSFER, OF COCAETHYLENE ACROSS THE HUMAN TERM PLACENTAL COTYLEDON PERFUSED IN-VITRO

Cocaethylene is produced by transesterification of cocaine in the pres ence of ethanol, and there is evidence that it is more neurotoxic than cocaine. Because many women of reproductive age use cocaine and becau se many cocaine users also consume alcohol, the fetal toxicology of co caethylene is of great concern, At the present time the placental tran sfer of cocaethylene has not been fully characterized, The objective o f this article was to measure the transfer of cocaethylene across the human term placenta, The transfer of cocaethylene was measured using t he in vitro dual perfusion of the human term placental cotyledon, Usin g a ''closed-circuit'' design, the extraction fraction of cocaethylene was measured to be 0.009 mu g/mL . min(-1) and the transfer fraction was measured to be 0.013 mu g/mL . min(-1), suggesting that the placen tal tissue retained some of the administered dose, Using an ''open cir cuit'' design, the clearance of the compound hy the placenta was found to be 78 +/- 14% that of antipyrine clearance. The metabolism of coca ethylene by the perfused placental cotyledon was also measured using a n ''open circuit'' design and was found to be negligible, These result s indicate that the placenta does not serve as a significant physical or metabolic barrier to cocaethylene transfer from mother to child, As compared to previously reported results, the transfer of this compoun d across the human placenta is similar to that of cocaine. Variability in placental handling of cocaethylene may therefore determine fetal e xposure to this compound. (C) 1997 Elsevier Science Inc.