Cocaine clearance by the human placenta perfused in vitro

Cocaine self-administration results in plasma concentration profiles similar to those seen in bolus drug dosing. However, previous studies measuring the transfer of cocaine across the placenta have used the in vitro perfusion of the human placental cotyledon with a constant drug concentration in the maternal circulation. Given that the human placenta can retain large amounts of an administered dose of cocaine, we hypothesized that the term placenta can buffer fetal exposure from high peak plasma concentrations of cocaine in the maternal circulation. Using the in vitro perfused human placental cotyledon, the clearance of cocaine by the placenta was measured under two conditions: (a) constant maternal concentration of cocaine; and (b) maternal cocaine concentration profile similar to a bolus dose administration. Cocaine clearance with a constant maternal concentration was 2.16 ± 0.37 mL/min and did not differ from the clearance with bolus dosing in the maternal circuit was 1.96 ± 0.63 mL/min (Student t-test, p>0.05). Therefore, the placenta's ability to retain large amounts of cocaine did not alter cocaine's ability to cross the placenta. In conclusion, the placenta does not effectively protect the fetus from high maternal peak plasma concentration by buffering cocaine transfer.