Drug accumulation in lung fluid of the fetal lamb after accumaternal or fetal administration

Abstract

The pharmacokinetic characteristics of the antiemetic drug metoclopramide and the antihistamine diphenhydramine have been determined in a chronically catheterized pregnant sheep preparation. Metoclopramide and diphenhydramine were administered by separate maternal and fetal intravenous infusions to a steady state as well as by maternal intravenous bolus dosing. Drug concentrations in the maternal and fetal plasma and the amniotic and tracheal fluids were measured by means of capillary gas-liquid chromatographic assay techniques. Both metoclopramide and diphenhydramine were excreted into tracheal fluid in substantial quantities. Tracheal metoclopramide concentrations were found to exceed fetal plasma levels by about fifteen-fold while diphenhydramine attained maximal excretion in tracheal fluid of about five times that seen in fetal plasma. Drug levels were observed to accumulate slowly in amniotic fluid and eventually to exceed tracheal concentrations. The markedly elevated concentrations of these drugs in fetal lung fluid suggests that the fetal lung may be an important route of drug distribution, elimination, and excretion.