Distribution and fate of nicotine in the rat fetus

[3H] (−)‐Nicotine was administered iv into pregnant Long‐Evans rats on day 19 of gestation or in three consecutive daily doses given on days 16 through 18 of gestation. The concentration of radioactivity and proportions of labeled compounds were determined at intervals from 5 min to 20 h after injection in maternal plasma and liver, decidua basalis, placenta, amniotic fluid, whole fetus, and fetal plasma, brain, lungs, heart, liver, adrenals, kidneys, gonads, and the stomach‐intestine‐spleen‐pancreas en bloc. Nicotine, cotinine, and other metabolites appeared in the fetus within 5 min of injection. The concentration of radioactivity in the fetal plasma exceeded that of the maternal plasma from 30 min through 20 h. Fetal liver had a greater proportion of radioactivity as nicotine than did maternal liver. Fetal plasma as well as most of the fetal tissues had a greater proportion of nicotine to metabolites than did the maternal plasma throughout the time period that was studied. By 60 min an equilibrium was established between maternal plasma and amniotic fluid with respect to concentration of radioactivity. This equilibrium was maintained through 20 h after single injections and also after the three daily injections. The proportions of nicotine to major metabolites were similar in maternal plasma and amniotic fluid at 4 h. The findings show that fetal rat tissues are exposed to levels of nicotine greater than those found in maternal plasma beginning within 30 min of the time nicotine enters the maternal circulation.