Brenda Knie

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 biotransformation of nicotine in the human term placenta. Nicotine transfer was studied by dually perfusing an isolated cotyledon of the human placenta in vitro. Nicotine metabolism to cotinine was investigated in intact tissue during perfusion and in placental microsomal fractions. Following 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 placenta (0.15 +/- 0.01 ng/ml/min). The steady-state maternal-to-fetal transfer 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. The observation that nicotine readily crosses the human placenta with no evidence of metabolism suggests that nicotine has the potential to cause adverse affects on the developing fetus.

Transfer of cocaine and benzoylecgonine across the perfused human placental cotyledon

OBJECTIVE Our aim was to measure the transfer of cocaine and its major metabolite benzoylecgonine across the human term placenta. STUDY DESIGN By means of in vitro perfusion of the human term placental cotyledon the transfer of these compounds was measured. RESULTS The steady-state maternal-to-fetal transfer of cocaine (0.18 +/- 0.05 microgram/ml/min) was significantly greater than benzoylecgonine transfer (0.02 +/- 0.01 microgram/ml/min) (p < 0.05). When the perfused tissue was analyzed 32% +/- 7% of the maternal cocaine dose was retained by the placental tissue, whereas only 12% +/- 12% of the maternal benzoylecgonine dose was retained by the placental compartment. CONCLUSIONS These results suggest (1) the placenta may serve as a depot for large amounts of cocaine, thus offering some degree of fetal protection after bolus administration; (2) fetal exposure may be prolonged by placental retention and subsequent release of cocaine and benzoylecgonine; and (3) benzoylecgonine does not cross the placenta as readily as does cocaine. Variability in placental handling of cocaine and benzoylecgonine may therefore determine fetal exposure to these agents.

Transfer of morphine across the human placenta and its interaction with naloxone

The purpose of this investigation was to measure the transfer rate and clearance of morphine across the placenta with and without naloxone. Term human placental cotyledons were perfused in vitro. The placenta was perfused with 50 ng/mL of morphine in the absence (n=4) and presence (n=5) of 100 ng/mL of naloxone. Maternal and fetal samples were collected. Students t-test or one-way repeated measures ANOVA were used for all comparisons. The maternal-to-fetal morphine transfer rate was 0.73+/-0.44 ng/mL/min in the morphine and 0.69+/-0.26 ng/mL/min in the morphine-naloxone experiments (p=0.89). The clearance of morphine was 0.89+/-0.39 mL/min without naloxone and 0.87+/-0.27 mL/min with naloxone (p=0.92). Final morphine concentrations in the morphine experiments were 9.78+/-6.17 ng/mL (maternal) and 3.43+/-2.14 ng/mL (fetal) and 10.04+/-3.89 ng/mL (maternal) and 4.16+/-1.64 ng/mL (fetal) in the morphine-naloxone experiments. Morphine readily crosses the term human placenta. Naloxone does not alter placental transfer or clearance of morphine, suggesting that transfer across the placental barrier is not altered by changes in vascular resistance. Placental retention of morphine prolongs fetal exposure to morphine.