TRANSPLACENTAL TRANSFER AND BIOTRANSFORMATION STUDIES OF NICOTINE IN THE HUMAN PLACENTAL COTYLEDON PERFUSED IN-VITRO

Our objective was to study the characteristics of transfer and biotran sformation of nicotine in the human term placenta. Nicotine transfer w as studied by dually perfusing an isolated cotyledon of the human plac enta in vitro. Nicotine metabolism to cotinine was investigated in int act tissue during perfusion and in placental microsomal fractions. Fol lowing the addition of nicotine (40 ng/ml) to the maternal side of the placenta, distribution into placental tissue (0.43 +/- 0.13 ng/ml/min ) was three times higher than transfer to the fetal side of the placen ta (0.15 +/- 0.01 ng/ml/min). The steady-state maternal-to-fetal trans fer of nicotine was approximately 90% that of antipyrine (a marker of flow-dependent transfer). There was no evidence of nicotine metabolism to cotinine by intact placental tissue or in microsomal fractions. Th e observation that nicotine readily crosses the human placenta with no evidence of metabolism suggests that nicotine has the potential to ca use adverse affects on the developing fetus.