Transplacental pharmacokinetics and maternal/fetal plasma concentrations of cocaine in pregnant macaques near term

Abstract

The transplacental pharmacokinetics of cocaine were studied in three pregnant rhesus monkeys (Macaca mulatta) at 150-154 days of pregnancy (term approximately 165 days). Animals were dosed intramuscularly with cocaine hydrochloride at 1 mg/kg, supplemented with a tritiated cocaine tracer. Plasma cocaine and its metabolite benzoylecgonine levels were determined after separation by HPLC and subsequent quantification by liquid scintillation spectrometry. Cocaine levels peaked in maternal blood within 10-20 min after dosing, and cocaine was detected in fetal blood within 5 min, reaching peak concentrations within 30-120 min. Mean maternal elimination half-lives (t1/2) for cocaine and benzoylecgonine were 1.2 +/- 0.5 hr and 12.4 +/- 6.6 hr (+/- SEM), respectively; fetal half-lives were 0.5 +/- 0.2 and 7.7 +/- 3.0 hr. Mean maternal residence times were 1.9 +/- 0.5 and 17.0 +/- 9.1 hr for cocaine and benzoylecgonine, respectively; fetal values were 2.1 +/- 0.2 and 11.6 +/- 3.5 hr. Total areas under the concentration versus time curves (AUCs) for cocaine and benzoylecgonine in maternal plasma were 360 +/- 38 and 585 +/- 260 (ng/ml) hr, respectively; fetal values were 104 +/- 29 and 262 +/- 61 (ng/ml) hr. Based on AUC comparisons for cocaine, fetal exposures are thus approximately one-third of maternal exposures, demonstrating that substantial exposure to cocaine does occur in utero.