Cocaine metabolites in the neonate: potential for toxicity

Recent reports indicate that cocaine metabolites have biologic activity and could be toxic. To explore this possibility, two studies were initiated. The first study aimed to define the distribution of cocaine species by quantifying levels of cocaine and its metabolites norcocaine, benzoylecgonine, and benzoylnorecgonine in newborn cord blood and meconium. The second study sought to determine whether they produced a clinical effect. Compared to cord blood, meconium had a greater number of metabolites and a higher concentration of cocaine metabolites, including the previously undetectable norcocaine and benzoylnorecgonine derivatives. Benzoylecgonine was the most common species found in both sources and was usually lower in concentration in blood. An inverse relation existed between meconium benzoylecgonine levels and the serum catabolic enzyme pseudocholinesterase, implying genetic variability in cocaine metabolism. To determine whether cocaine and/or its metabolites could be linked to a distinct clinical state, a second study focusing on newborn behavior was performed with an independent large cohort of cocaine-exposed infants. Neonates with increased signs of "neuroexcitation" had benzoylecgonine and no cocaine in urine, whereas lethargic neonates had detectable urinary cocaine. These findings support the hypothesis that cocaine metabolites, especially benzoylecgonine, may play a role in altering newborn behavior and produce a clinical syndrome distinct from that related to the parent compound.