Although the use of medication during pregnancy is common, information on exposure to the developing fetus and potential teratogenic effects is often lacking. This study used a rat model to examine the placental transfer of three small-molecule drugs with molecular weights ranging from approximately 300 to 800 Da with different physicochemical properties. Time-mated Sprague Dawley (Hsd:SD) rats aged 11-13 weeks were administered either glyburide, rifaximin, or fentanyl at gestational day 15. Maternal blood, placentae, and fetuses were collected at 5 min, 30 min, 1 h, 4 h, 8 h, 24 h, 48 h, and 96 h post-dose. To characterize the rate and extent of placental drug transfer, we calculated several pharmacokinetic parameters such as maximum concentration (Cmax), time to maximum concentration (Tmax), area under the concentration-time curve (AUC), half-life (t1/2), clearance (CL), and volume of distribution (Vd) for plasma, placenta, and fetus tissues. The results indicated showed that fetal exposure was lowest for glyburide, accounting for only 2.2 % of maternal plasma exposure as measured by their corresponding AUC ratio, followed by rifaximin (37.9 %) and fentanyl (172.4 %). The fetus/placenta AUC ratios were found to be 10.7 % for glyburide, 11.8 % for rifaximin, and 39.1 % for fentanyl. These findings suggest that although the placenta acts as a protective shield for the fetus, the extent of protection varies for different drugs and depends on factors such as molecular weight, lipid solubility, transporter-mediated efflux, and binding to maternal and fetal plasma proteins.
Keywords: Fentanyl; Fetus; Glyburide; Pharmacokinetic analysis; Placenta; Pregnancy; Rifaximin.
Published by Elsevier Inc.