Pharmacokinetics of cocaine in maternal and fetal rhesus monkeys at mid-gestation

Abstract

We compared pharmacokinetics of cocaine and its metabolite, benzoylecgonine, in pregnant rhesus monkeys and their fetuses at mid-gestation: 1) after a single intravenous dose of cocaine, 2) after a single oral dose of cocaine, 3) after the last oral cocaine administration of a 50-day-long chronic cocaine treatment, and 4) on the last day of a 50-day-long chronic treatment with five daily intravenous cocaine injections. We found that intravenous administrations of cocaine produced maximal maternal levels of benzoylecgonine below the plasma levels for cocaine. In contrast, oral administrations resulted in the maximal maternal plasma levels of this metabolite significantly above those of cocaine. The bioavailability of the orally administered cocaine was calculated as 25%. Cocaine was detectable in the fetal plasma at maximal levels of approximately 1/5 of peak maternal levels for both single intravenous and single oral administrations. The maximal plasma levels of benzoylecgonine for the fetuses of the intravenously treated mothers were close to those of cocaine, whereas peak levels of this metabolite in the plasma of the fetuses of the mothers receiving the oral treatments were above those of cocaine. The chronic treatments resulted in significantly higher maximal levels of cocaine in the fetal circulation compared with those produced by single drug administrations.