Tissue distribution of cocaine in the pregnant rat.
Cocaine hydrochloride was administered by single intraperitoneal (IP) doses to pregnant rats at day 18 or 19 of gestation. Plasma and tissue cocaine and norcocaine concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic analysis of concentration versus time data showed rapid distribution of cocaine and its metabolite to maternal and fetal tissues. The area under the cocaine concentration versus time curve (AUC) in fetus compared to maternal plasma was 3.33. The half-life of cocaine in the maternal plasma and fetus was 46 and 55 minutes, respectively, similar to values reported for cocaine elimination half-life in human plasma. The order of cocaine concentrations was placenta greater than fetal liver greater than maternal heart greater than whole fetus greater than fetal brain greater than maternal brain = maternal plasma. Norcocaine concentrations were usually less than 20% of cocaine concentrations in plasma and tissues. These results support extensive fetal exposure to cocaine following administration to pregnant rodents. Pharmacodynamic studies of cocaine in pregnancy should consider the effects of the drug on the developing fetus.
DeVane
C L
CL
Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville 32610.
Simpkins
J W
JW
Miller
R L
RL
Braun
S B
SB
D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D009206:Myocardium / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
C008671:norcocaine; D003042:Cocaine