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  • Title: Pharmacokinetics and metabolism of cocaine in maternal and fetal guinea pigs.
    Author: Sandberg JA, Murphey LJ, Olsen GD.
    Journal: Neurotoxicology; 1995; 16(1):169-77. PubMed ID: 7603638.
    Abstract:
    The pharmacokinetics and metabolism of cocaine (COC) were determined in late gestation maternal and fetal guinea pigs. After a single i.v. dose of 2-12 mg/kg, the average +/- SD total body clearance of COC was 59 +/- 16 ml/min/kg and was not dose dependent. However, volume of distribution was 2.1 and 3.9 l/kg, mean resident time (MRT) was 42 and 57 min, and elimination half-life was 34 and 49 min at the 2 and 4 mg/kg dose of COC, respectively. With the exception of an increased MRT, the pharmacokinetics were similar after s.c. COC administration. Benzoylecgonine (BE) and benzoylnorecgonine (BN) were major and persistent metabolites. Norcocaine (NOR) concentrations were low and transient. After chronic maternal administration of 6 mg/kg COC s.c., there was no difference between maternal and fetal plasma COC concentrations one hour after the last injection, but COC and BN accumulated in amniotic fluid. Examination of in vitro metabolism of COC in fetal and maternal guinea pig hepatic microsomes demonstrated minimal fetal N-demethylation and induction of maternal N-demethylation by chronic COC exposure. The minimal fetal N-demethylation suggest BN seen previously in vivo after chronic maternal COC administration resulted from maternal formation of NOR and subsequent maternal and/or fetal hydrolysis to BN.
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