Metabolism of cocaine by human placentas: implications for fetal exposure

To assess placental metabolism of cocaine, placentas were obtained at the time of delivery and the microsomes were extracted by ultracentrifugation within 2 hours. Placental microsomes were cultured with cocaine at physiologic plasma concentrations similar to those of cocaine users (0.75 micrograms/ml). Two control groups were established. In the first group an anticholinesterase was added to the culture to suppress enzyme activity, and in the second cocaine was cultured alone without placental microsomes to obtain baseline spontaneous conversion of the drug. The results indicate that cocaine is biotransformed by the human placenta, presumably by cholinesterase activity. This suggests that the placenta may provide a moderate degree of protection from cocaine-induced morbidity, such as abruptio placentae and fetal growth retardation, by converting cocaine into less active metabolites. These results also have pharmacogenetic implications because cholinesterase activity varies among individuals. Hence placentas that cannot transform the drug may place the conceptus at greater risk of developmental abnormalities.