Dose-related differences in the distribution of cocaine in the maternal-fetoplacental compartments in rats.
Our goals were to examine whether a high dose of cocaine to causing CNS toxic manifestations in the pregnant rats influences the delivery of cocaine to the fetus, and whether the non-placental compartments have a significant role in the distribution of cocaine to the fetal tissues. Either a low or high dose of cocaine was infused intravenously to near-term pregnant rats. Arterial blood pressure and heart rate were monitored. Cardiac output and uterine and placental blood flows were measured by using radiolabeled microspheres. Plasma and tissue samples were obtained from the mother, placenta, and fetus and analyzed for cocaine and its metabolites via capillary gas chromatography/mass spectrometry. A high dose of cocaine induced convulsions that were accompanied by increased arterial blood pressure and decreased uteroplacental blood flow. However, the distribution pattern of cocaine and metabolites in the mother and fetus were similar between the high and low dose groups. Considerable amounts of cocaine and its metabolites were in the placenta. Previously ignored non-placental tissues, such as the amnion and myometrium appear to be a significant source for cocaine accumulation in the fetus.
Morishima
H O
HO
Departments of Anesthesiology and Psychiatry, College of Physicians and Surgeons, Columbia University, 622 West, 168th Street, New York, NY 10032, USA. hom2@columbia.edu
Okutomi
T
T
Whittington
R A
RA
Cooper
T B
TB
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003042:Cocaine