Maternal and fetal brain and plasma levels of cocaine and benzoylecgonine after acute or chronic maternal intravenous administration of cocaine.
The effect of repeated i.v. administration of cocaine HCl (1.5, 3 or 6 mg/kg daily) from gestational day 8 through gestational day 18 was studied on maternal and litter parameters in the pregnant female Sprague-Dawley rat. These doses of cocaine had no significant effect on maternal weight gain or nutritional intake and did not significantly affect litter size. Levels of cocaine and its metabolite benzoylecgonine in the brain and plasma of the dams and their fetuses were measured on gestational day 18 at 1, 5, 20 or 60 min after a single injection or 11 daily i.v. injections of cocaine (6 mg/kg). The shape of the time courses for cocaine differed somewhat between dams and fetuses, with fetal plasma concentrations of cocaine initially being lower than those of their dams and then by 5 min becoming equivalent to those of their dams. Although plasma concentrations of cocaine soon equilibrated between dams and fetuses, plasma concentrations of benzoylecgonine did not. Interestingly, brain concentrations of cocaine did not differ between dams and fetuses. The most remarkable finding was that the relative distribution of cocaine between brain and plasma differed after chronic vs. acute treatment, with a relative shift in the distribution of cocaine from plasma to the brain in the fetuses, and with the exception of the earliest time point measured, in the dams after repeated dosing.
Robinson
S E
SE
Department of Pharmacology and Toxicology, Virginia Commonwealth University Medical College of Virginia, Richmond.
Enters
E K
EK
Jackson
G F
GF
Chinchilli
V M
VM
Maher
J R
JR
McDowell
K P
KP
Allen
H M
HM
Guo
H
H
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D007275:Injections, Intravenous; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
C005618:benzoylecgonine; D003042:Cocaine