Transplacental pharmacokinetics of cocaine and benzoylecgonine in plasma and hair of rhesus monkeys.
There is large variability in the rate and extent of fetal damage from cocaine in humans; however, the sources of such variability are not presently known. In order to study the relationship between maternal cocaine pharmacokinetics at the end of pregnancy and maternal or infant cocaine and benzoylecgonine hair concentrations at birth, ten rhesus monkeys were administered cocaine intramuscularly throughout pregnancy. Cocaine and benzoylecgonine hair concentrations were determined at birth and correlated with maternal pharmacokinetics during pregnancy. There were no correlations between either maternal cocaine Cmax or AUC0-infinity and maternal and infant hair cocaine or benzoylecgonine concentrations. There were no significant correlations between maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax (r = 0.60; P = 0.07). No correlations existed between infant hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine Cmax (r = 0.30; P = 0.40). Also, no correlation was found between maternal cocaine dose and maternal or infant cocaine and benzoylecgonine hair concentrations. In comparison to toxicants such as nicotine and carbon monoxide for which there is a good correlation between maternal systemic exposure and neonatal concentrations, the lack of a similar relationship for cocaine is consistent with the role of the placenta in contributing to the variability in the amounts of cocaine reaching the fetus and hence, potentially to the risk of adverse fetal outcome.
Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.
B
B
Bailey
P
P
Morris
K I
KI
McMartin
J
J
Klein
H M
HM
Duhart
M P
MP
Gillam
Z
Z
Binienda
W
W
Slikker
M G
MG
Paule
G
G
Koren
D000818:Animals; D000831:Animals, Newborn; D003042:Cocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006197:Hair / Q000378:metabolism*; D016014:Linear Models; D008253:Macaca mulatta; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
C005618:benzoylecgonine; D003042:Cocaine