Distribution of cocaine and metabolites in the pregnant rat and fetus in achronic subcutaneous injection model

We examined the distribution of cocaine and its metabolites benzoylecgonine (BE) and norcocaine (NOR) in pregnant Sprague-Dawley rats and fetuses foll owing twice-daily subcutaneous (s.c.) injections of 20 mg/kg cocaine HCl fr om gestational day (GD) 8 through GD 20. On GD 21, the animals received a s ingle injection and maternal trunk blood, fetal blood, fetal brains, and am niotic fluid were collected 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, or 1 2 h later for cocaine and metabolite analyses by high-performance liquid ch romatography (HPLC) with UV detection. The highest concentrations of cocain e and BE were detected in maternal plasma at 1 h and 4 h respectively. Coca ine 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 g iven both cocaine injections on GD 21 and sacrificed 2 h later. Benzoylecgo nine concentrations were increased in fetal plasma, fetal brain, and amniot ic fluid when compared with the 2-h results following a single cocaine trea tment. Moreover, NOR, which had not been previously detected, was now measu rable in the amniotic fluid. (C) 1999 Elsevier Science Inc. All rights rese rved.