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 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.
Morishima
H O
HO
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, USA. hom2@columbia.edu
Okutomi
T
T
Ishizaki
A
A
Zhang
Y
Y
Cooper
T B
TB
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
C005618:benzoylecgonine; D003042:Cocaine