Elimination of cocaine by pregnant sheep following single or multiple exposures.
To test the hypothesis that chronic exposure to cocaine would alter drug elimination in pregnant and fetal sheep compared to a single exposure, we administered intravenous cocaine HCl to 8 pregnant sheep daily as a bolus, followed by a 2-h infusion beginning at gestational age 75 days. Eight additional animals received an equivalent volume of saline. Three days after maternal and fetal catheter placement on day 125, ewes in both groups received cocaine HCl, 2 mg/kg, as a bolus. Maternal and fetal plasma samples were serially obtained and analyzed for cocaine and benzoylecognine. Cocaine half-life in the ewes and fetuses exposed to cocaine was no different from that in animals exposed to saline. We conclude that cocaine is rapidly metabolized in pregnant sheep and that chronic administration does not alter drug clearance.
Burchfield
D J
DJ
Department of Pediatrics, Colleges of Medicine, University of Florida, Gainesville, Florida 32610, USA. burchdj@peds.ufl.edu
Tebbett
I R
IR
Anderson
K J
KJ
D000818:Animals; D002404:Catheterization / Q000379:methods; D002408:Catheters, Indwelling; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005865:Gestational Age; D006207:Half-Life; D007260:Infusion Pumps; D007275:Injections, Intravenous; D008431:Maternal-Fetal Exchange; D008657:Metabolic Clearance Rate / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011897:Random Allocation; D012756:Sheep; D013997:Time Factors
C005618:benzoylecgonine; D003042:Cocaine