Cocaine and metabolite concentrations in the fetal guinea pig after chronic maternal cocaine administration.
To determine the disposition of cocaine (COC) and metabolites after chronic COC exposure in the late gestation guinea pig, six time-bred Dunkin-Hartley guinea pigs were given 10 daily 6 mg/kg COC s.c. injections from day 50 of gestation. Maternal blood and urine, fetal cord blood, and brain and amniotic fluid were collected 1 hr after the last injection. There was no difference between maternal and fetal plasma COC concentrations. This may be due to the combined effect of lower protein binding and ion trapping of COC in the fetus. Benzoylecgonine was higher in maternal plasma, but benzoylnorecgonine was higher in fetal plasma. COC brain-to-plasma ratios were similar in the dam and fetus. Benzoylecgonine was the only metabolite that could be detected in the brain, but levels were too low to quantitate. COC accumulated 3 to 4 times plasma concentrations in the amniotic fluid and was directly proportional to fetal plasma COC concentrations. Benzoylnorecgonine in amniotic fluid accumulated to 2 times fetal plasma levels. The in vitro half-life of COC in amniotic fluid was 30 times longer than plasma elimination half-life in vivo. The high level and long duration of COC in amniotic fluid serve as a reservoir for prolonged fetal COC exposure.
Sandberg
J A
JA
Department of Pharmacology, School of Medicine, Oregon Health Sciences University, Portland.
Olsen
G D
GD
D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000196:embryology; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000493:pharmacokinetics; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006168:Guinea Pigs; D008012:Lidocaine / Q000493:pharmacokinetics; D008431:Maternal-Fetal Exchange; D011247:Pregnancy
C008671:norcocaine; C005618:benzoylecgonine; D008012:Lidocaine; D003042:Cocaine; C012209:benzoylnorecgonine