title: The disposition of benzoylecgonine in maternal and fetal rats.
abstract: We tested our hypothesis that pregnancy alters the pharmacokinetic profile of benzoylecgonine, and that this metabolite accumulates in the fetus longer than in the mother. Chronically catheterized near-term pregnant and nonpregnant female Sprague-Dawley rats received an intravenous infusion of benzoylecgonine over a period of 30 min. Adult or fetal blood and tissue samples were obtained either at the end of the infusion or 6 h postinfusion for analysis of benzoylecgonine and other cocaine metabolite concentrations via gas chromatography/mass spectrometry (GC/MS). Pregnancy altered benzoylecgonine pharmacokinetics. At the end of the infusion, benzoylecgonine concentration in the fetal plasma was markedly lower than in the maternal plasma with a fetal/maternal ratio of 0.14+/-0.01. A significantly lower concentration of benzoylecgonine was found in both maternal and fetal brain at 0 h postinfusion, with tissue/plasma concentration ratios of 0.04 and 0.24, respectively, suggesting that benzoylecgonine does not readily penetrate into the brain. At 6 h, the fetal concentration of benzoylecgonine was significantly higher than in the corresponding maternal blood and tissues. Ecgonine methyl ester, a metabolite of benzoylecgonine was found in the maternal liver, but not in the fetus. In addition, the amniotic fluid concentration of benzoylecgonine became significantly higher in the 6-h postinfusion samples as compared to the end of infusion value, suggesting that repeated intrauterine exposure to cocaine may cause an accumulation of benzoylecgonine in the fetus.
authors: Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, USA. hom2@columbia.edu
authors: H O
authors: HO
authors: Morishima
authors: T
authors: T
authors: Okutomi
authors: A
authors: A
authors: Ishizaki
authors: Y
authors: Y
authors: Zhang
authors: T B
authors: TB
authors: Cooper
mesh_terms: D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D014018:Tissue Distribution
chemical_list: C005618:benzoylecgonine; D003042:Cocaine