Fetal and maternal cocaine levels peak rapidly following intragastric administration in the rat.
On gestation day 22, plasma levels of cocaine and its metabolite, benzoylecgonine (BE), were determined over 90 min following either 30 or 60 mg/kg cocaine given via intragastric intubation to Wistar rats which had been given daily cocaine intubations since day 8 of pregnancy. Cocaine levels peaked at 15 min in both the maternal and fetal circulations. Sixty mg/kg produced a peak plasma level of 5384 +/- 594 ng/ml in the dam and 2966 +/- 503 ng/ml in the fetus. Maternal levels of cocaine were higher than fetal levels for the first fifteen min. Thereafter, maternal levels decreased more quickly than fetal such that at 30-90 min, fetal levels were higher than maternal levels. Cocaine levels also peaked at 15 min in fetal brain. At 90 min, however, fetal brain had between 26 and 42% more cocaine than fetal plasma. Therefore, fetal brain exposure to cocaine is somewhat prolonged. BE levels were less predictable. Together, these data indicate that the intragastric route of administration results in rapid uptake of cocaine by blood and produces highly reproducible, pharmacologically relevant levels of cocaine in maternal and fetal plasma and brain. In addition, the placenta does not act as a barrier to the delivery of cocaine to the fetus.
Dow-Edwards
D
D
State University of New York Health Science Center.
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000502:physiology*; D008657:Metabolic Clearance Rate / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
C005618:benzoylecgonine; D003042:Cocaine