Distribution of cocaine and metabolites in the pregnant rat and fetus in a chronic subcutaneous injection model.
We examined the distribution of cocaine and its metabolites benzoylecgonine (BE) and norcocaine (NOR) in pregnant Sprague-Dawley rats and fetuses following twice-daily subcutaneous (s.c.) injections of 20 mg/kg cocaine HCl from gestational day (GD) 8 through GD 20. On GD 21, the animals received a single injection and maternal trunk blood, fetal blood, fetal brains, and amniotic fluid were collected 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, or 12 h later for cocaine and metabolite analyses by high-performance liquid chromatography (HPLC) with UV detection. The highest concentrations of cocaine and BE were detected in maternal plasma at 1 h and 4 h respectively. Cocaine peaked at 2 h and BE at 4 h in both fetal plasma and brain. In amniotic fluid, cocaine levels peaked at 2 h, but the highest BE levels were found at 8 h postinjection. An additional group of chronically treated dams was given both cocaine injections on GD 21 and sacrificed 2 h later. Benzoylecgonine concentrations were increased in fetal plasma, fetal brain, and amniotic fluid when compared with the 2-h results following a single cocaine treatment. Moreover, NOR, which had not been previously detected, was now measurable in the amniotic fluid.
Collins
L M
LM
Department of Psychology, Neuroscience and Behavior Program, University of Massachusetts, Amherst 01003-7710, USA.
Pahl
J A
JA
Meyer
J S
JS
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
C008671:norcocaine; C005618:benzoylecgonine; D003042:Cocaine