INFLUENCE OF MATERNAL BLOOD-FLOW ON THE PLACENTAL-TRANSFER OF 3 OPIOIDS - FENTANYL, ALFENTANIL, SUFENTANIL

The placental transfer of three opioids used in peridural analgesia, f entanyl, alfentanil and sufentanil, and two reference substances, anti pyrine and H2O, was determined ex vivo in the human placental cotyled on system. (1) In the first set of experiments, the infusion rates wer e constant and fixed at physiological flow rates. Under these conditio ns, the magnitude of the materno-fetal transfer was in the following o rder: H2O = antipyrine = fentanyl > alfentanil > sufentanil. No parti cular influence of molecular weight, lipophilia, pKa or the degree of ionization could be discerned. (2) In the second set of experiments, t he influence of different flow rates, reflecting various pathophysiolo gical conditions, was examined. There was a linear relationship betwee n the maternal flow and the materno-fetal transfer of the three opioid s. On the other hand, for antipyrine and tritiated water, the relation ship was logarithmic, a difference attributed to the marked lipophilia of the opioids. (3) At high maternal flow rates, saturation was obser ved for all five substances due to the short duration of contact with the membrane. There were logarithmic relationships between the materna l flow and the materno-fetal transfer. (4) These findings emphasize th e importance of the lipophilic and hydrophilic characteristics of drug s on placental transfer, especially in the event of fluctuations in ma ternal flow.