Elimination of cocaine by pregnant sheep following single or multiple exposures

To test the hypothesis that chronic exposure to cocaine would alter drug el imination in pregnant and fetal sheep compared to a single exposure, we adm inistered intravenous cocaine HCl to 8 pregnant sheep daily as a bolus, fol lowed by a 2-h infusion beginning at gestational age 75 days. Eight additio nal animals received an equivalent volume of saline. Three days after mater nal and fetal catheter placement on day 125, ewes in both groups received c ocaine HCl, 2 mg/kg, as a bolus. Maternal and fetal plasma samples were ser ially obtained and analyzed for cocaine and benzoylecognine. Cocaine half-l ife in the ewes and fetuses exposed to cocaine was no different from that i n animals exposed to saline. We conclude that cocaine is rapidly metabolize d in pregnant sheep and that chronic administration does not alter drug cle arance.