Abstract

The disposition of 14C-quazepam following a single 5-mg/kg po dose was studied at the postembryonic period (day 12 of pregnancy) and near-term (day 18 of pregnancy). In both 12- and 18-day pregnant mice, radioactivity from the quazepam dose was widely distributed in the maternal tissues, with the highest levels in the liver and kidneys. At the time points analyzed (1, 5, and 24 hr post-dose), radioactivity levels in the fetus were consistently 44% of the maternal plasma levels in 12-day pregnant mice. In 18-day pregnant mice, fetal radioactivity levels at these time points were consistently equal to or slightly greater than maternal plasma levels. This indicates that radioactivity was taken up and eliminated from fetal tissues at rates that were reasonably similar to those in corresponding maternal tissues. No accumulation of radioactivity was observed in the fetus or in maternal tissues in either the 12-day or the 18-day pregnant mice. In 18-day pregnant mice, concentrations of quazepam and its metabolites were measured either by gas-liquid chromatography or thin layer radiochromatography. In the maternal plasma, concentrations of quazepam, its first-formed metabolite, 2-oxoquazepam, and 3-hydroxy-2-oxoquazepam were relatively low at all time points; levels of N-desalkyl-2-oxoquazepam and 3-hydroxy-N-desalkyl-2-oxoquazepam (HDOQ) were much higher. Fetal levels of unchanged drug and metabolites were generally less than or equal to maternal plasma levels, except for HDOQ levels, which were higher in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)