Diazepam in Early Human Pregnancy

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Abstract
The transfer of diazepam and N-demethyldiazepam across the placenta in early human pregnancy is studied in a group of 12 patients after a single dose, and in a group of 7 patients after the continued use of diazepam for up to a month. After a single dose the feto-maternal ratio of the diazepam concentrations is 1.2, while after continued use it is 0.4. The main reason for this difference is probably the incomplete distribution of diazepam after a single dose at the time the samples are taken. The transfer of N-demethyl-diazepam across the placenta occurs just as easily and the feto-maternal ratio after continued treatment is 0.4, too. The concentration of N-demethyldiazepam in the fetal liver is higher than any other concentration measured and this could constitute indirect evidence of metabolism in the fetal liver. The concentrations of diazepam and N-demethyldiazepam in fetal tissues are at a level comparable to the concentration of diazepam that has a damaging effect on cells in cellular cultures.

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