Transfer and Uptake of Alfentanil in the Human Placenta During In Vitro Perfusion

Alfentanil, a short-acting lipophilic opioid, is used for labor analgesia and cesarean section and may cause neonatal depression. However, direct placental alfentanil transfer has not been studied. We measured placental alfentanil transfer and uptake during in vitro perfusion. Placenta lobules from healthy parturients were perfused with biophase at pH 7.4,95%:5% O2:CO2. Maternal to fetal (MTF, n = 10) and fetal to maternal (FTM, n = 10) transfer were examined during perfusion with alfentanil 10 ng/mL, antipyrine, and creatinine for 1 h. Thereafter, both MTF and FTM placentas were assayed for alfentanil content (n = 3), or perfused with biophase for 1 h to determine drug washout and then assayed for alfentanil content (n = 3). After the 1 h washout, the remaining MTF placentas (n = 4) were then perfused MTF with high-dose alfentanil 1000 ng/mL to assess saturability of placental transfer. The remaining FTM placentas (n = 4) were then perfused with alfentanil 10 ng/mL in the MTF direction to verify that the same alfentanil transfer characteristics found between placentas were valid when the direction of drug transfer was reversed in the same placenta. Alfentanil was rapidly transferred (<5 min) across the placenta both MTF and FTM. During MTF transfer, fetal effluent reached a plateau at 2.2 ng/mL between 35 and 55 min, and was unmeasurable 30 min into washout. During FTM transfer, maternal effluent reached a plateau at 1.9 ng/mL at 25–45 min, and was absent after 20–45 min of washout. Alfentanil clearance, clearance index, and transfer index were similar for the two concentrations and were not influenced by perfusion direction in either separate placentas or within the same placenta. Placental tissue alfentanil content was lower than perfusate alfentanil concentration. The rapid transfer and plateau of alfentanil, equal transfer rate MTF and FTM, and the nonsaturability of clearance and transfer indices suggest that alfentanil transfer occurs passively in the human placenta. The rapid placental transfer and washout of alfentanil together with low placental tissue uptake should be considered when administering alfentanil if delivery is imminent. (Anesth Analg 1994;79:1089–93)