The disposition of benzoylecgonine in maternal and fetal rats

We tested our hypothesis that pregnancy alters the pharmacokinetic profile of benzoylecgonine, and that this metabolite accumulates in the fetus longe r than in the mother. Chronically catheterized near-term pregnant and nonpr egnant female Sprague-Dawley rats received an intravenous infusion of benzo ylecgonine 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 an alysis of benzoylecgonine and other cocaine metabolite concentrations via g as chromatography/mass spectrometry (GC/MS). Pregnancy altered benzoylecgon ine pharmacokinetics. At the end of the infusion, benzoylecgonine concentra tion in the fetal plasma was markedly lower than in the maternal plasma wit h a fetal/maternal ratio of 0.14 +/-0.01. A significantly lower concentrati on of benzoylecgonine was found in bath maternal and fetal brain at 0 h pos tinfusion, with tissue/plasma concentration ratios of 0.04 and 0.24, respec tively, suggesting that benzoylecgonine does not readily penetrate into the brain. At 6 h, the fetal concentration of benzoylecgonine was significantl y higher than in the corresponding maternal blood and tissues. Ecgonine met hyl ester, a metabolite of benzoylecgonine was found in the maternal liver, but not in the fetus. In addition, the amniotic fluid concentration of ben zoylecgonine became significantly higher in the 6h postinfusion samples as compared to the end of infusion value, suggesting that repeated intrauterin e exposure to cocaine may cause an accumulation of benzoylecgonine in the f etus. (C) 2001 Elsevier Science Inc. All rights reserved.