Assessment of biotransformation during transfer of propoxyphene and acetaminophen across the isolated perfused human placenta.

The purpose of this investigation was to assess the extent of biotransformation of drugs by the human placenta during their transfer from the maternal to the fetal circulation. Propoxyphene was used to determine N-demethylation, and acetaminophen served as a substrate for glucuronide and sulfate conjugation. Human full-term placentae were dually perfused in vitro, with one or the other drug being added to the maternal circulation. Propoxyphene and acetaminophen concentrations reached an essentially constant fetal/maternal ratio within 1 hour, with a half-time of about 20 minutes. The concentrations of both drugs in the placental tissues were higher than in the perfusion fluids; this accumulation was particularly pronounced in the case of propoxyphene. No metabolites of either drug were found in the maternal or fetal circulations, but norporpoxyphene, the N-demethylated metabolite of propoxyphene, was detected in placental tissue.