title: The transfer, of cocaethylene across the human term placental cotyledon perfused in vitro.
abstract: Cocaethylene is produced by transesterification of cocaine in the presence of ethanol, and there is evidence that it is more neurotoxic than cocaine. Because many women of reproductive age use cocaine and because many cocaine users also consume alcohol, the fetal toxicology of cocaethylene is of great concern. At the present time the placental transfer of cocaethylene has not been fully characterized. The objective of this article was to measure the transfer of cocaethylene across the human term placenta. The transfer of cocaethylene was measured using the in vitro dual perfusion of the human term placental cotyledon. Using a "closed-circuit" design, the extraction fraction of cocaethylene was measured to be 0.009 microgram/mL.min-1 and the transfer fraction was measured to be 0.013 microgram/mL.min-1, suggesting that the placental tissue retained some of the administered dose. Using an "open circuit" design, the clearance of the compound by the placenta was found to be 78 +/- 14% that of antipyrine clearance. The metabolism of cocaethylene by the perfused placental cotyledon was also measured using an "open circuit" design and was found to be negligible. These results 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 compound across the human placenta is similar to that of cocaine. Variability in placental handling of cocaethylene may therefore determine fetal exposure to this compound.
authors.affiliation: Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Simone
authors.forename: B M
authors.initials: BM
authors.lastname: Byrne
authors.forename: L O
authors.initials: LO
authors.lastname: Derewlany
authors.forename: M
authors.initials: M
authors.lastname: Oskamp
authors.forename: G
authors.initials: G
authors.lastname: Koren
mesh_terms: D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: C066444:cocaethylene; D003042:Cocaine