Transfer of cocaine and benzoylecgonine across the perfused human placental cotyledon.
OBJECTIVE
Our aim was to measure the transfer of cocaine and its major metabolite benzoylecgonine across the human term placenta.


METHODS
By means of in vitro perfusion of the human term placental cotyledon the transfer of these compounds was measured.


RESULTS
The steady-state maternal-to-fetal transfer of cocaine (0.18 +/- 0.05 microgram/ml/min) was significantly greater than benzoylecgonine transfer (0.02 +/- 0.01 microgram/ml/min) (p < 0.05). When the perfused tissue was analyzed 32% +/- 7% of the maternal cocaine dose was retained by the placental tissue, whereas only 12% +/- 12% of the maternal benzoylecgonine dose was retained by the placental compartment.


CONCLUSIONS
These results suggest (1) the placenta may serve as a depot for large amounts of cocaine, thus offering some degree of fetal protection after bolus administration; (2) fetal exposure may be prolonged by placental retention and subsequent release of cocaine and benzoylecgonine; and (3) benzoylecgonine does not cross the placenta as readily as does cocaine. Variability in placental handling of cocaine and benzoylecgonine may therefore determine fetal exposure to these agents.
Simone
C
C
Division of Clinical Pharmacology and Toxicology, University of Toronto, Ontario, Canada.
Derewlany
L O
LO
Oskamp
M
M
Knie
B
B
Koren
G
G
D001692:Biological Transport; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D009294:Narcotics / Q000493:pharmacokinetics*; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D009294:Narcotics; C005618:benzoylecgonine; D003042:Cocaine