Placental transfer of diphenhydramine in chronically instrumented pregnant sheep.
To study the placental transfer and pharmacokinetics of the H1 receptor blocker, diphenhydramine [2-(diphenylmethoxy)-N,N-dimethylethylamine], 100 mg of the drug was administered to four pregnant sheep (122-129 d gestation) by intravenous injection through catheters chronically implanted in the ewe and fetus. Rapid placental transfer occurred, with peak fetal plasma concentrations occurring within 5 min after injection. The fetal-maternal ratio of the area under the plasma concentration versus time curves averaged 0.85, indicating significant fetal exposure to the drug. The average apparent terminal elimination half-life in the ewe (52 min) was not significantly different from that obtained in the fetus (46 min). The maternal total body clearance was 3.6 L X h-1 X kg-1, and the volume of distribution at steady state was 3.2 L/kg. In summary, this study demonstrates rapid and extensive placental transfer of diphenhydramine after maternal drug administration. Since placental permeability to lipid-soluble compounds does not differ greatly in different species, it is likely that a similar situation exists in humans.
D000818:Animals; D004155:Diphenhydramine / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000378:metabolism; D005865:Gestational Age; D007700:Kinetics; D008431:Maternal-Fetal Exchange; D010100:Oxygen / Q000097:blood; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012756:Sheep
D004155:Diphenhydramine; D010100:Oxygen