The disposition of cocaethylene in rat maternal, placental, and fetal compartments.
OBJECTIVE
The aim of this project was to examine the disposition of maternally administered cocaethylene in the fetus.


METHODS
Pregnant rats with long-term catheter placement received an intravenous infusion of cocaethylene during a period of 30 minutes. At either the completion of the infusion or 6 hours after the infusion the fetuses were delivered by hysterotomy. Maternal and fetal blood and major tissue samples were obtained for assays of cocaethylene and its metabolites.


RESULTS
Cocaethylene was present in all samples obtained at the end of the infusion, but after 6 hours it was no longer detectable in the maternal and fetal systemic circulations. However, a substantial amount of cocaethylene was still present in the placenta on both the maternal and fetal sides, with the concentration on the maternal side being higher, indicating that the placenta stores cocaethylene. At the end of the infusion benzoylecgonine was found in all samples and the maternal concentrations were higher than the corresponding fetal concentrations. This order was reversed 6 hours after infusion. Extremely high concentrations of cocaethylene and benzoylecgonine were found in the amnion.


CONCLUSIONS
These results suggest that the placenta limits the transfer of cocaethylene to the fetus. The high affinity of this compound for extraplacental sites cannot be ignored.
D000650:Amnion / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D009206:Myocardium / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley