Drug Interactions at the Human Placenta: What is the Evidence?
Open Access
- 1 January 2012
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Pharmacology
- Vol. 3, 27396
- https://doi.org/10.3389/fphar.2012.00126
Abstract
Pregnant women (and their fetuses) are treated with a significant number of prescription and non-prescription medications. Interactions among those drugs may affect their efficacy and toxicity in both mother and fetus. Whereas interactions that result in altered drug concentrations in maternal plasma are detectable, those involving modulation of placental transfer mechanisms are rarely reflected by altered drug concentrations in maternal plasma. Therefore, they are often overlooked. Placental-mediated interactions are possible because the placenta is not only a passive diffusional barrier, but also expresses a variety of influx and efflux transporters and drug-metabolizing enzymes. Current data on placental-mediated drug interactions are limited. In rodents, pharmacological or genetic manipulations of placental transporters significantly affect fetal drug exposure. In contrast, studies in human placentae suggest that the magnitude of such interactions is modest in most cases. Nevertheless, under certain circumstances, such interactions may be of clinical significance. This review describes currently known mechanisms of placental-mediated drug interactions and the potential implications of such interactions in humans. Better understanding of those mechanisms is important for minimizing fetal toxicity from drugs while improving their efficacy when directed to treat the fetus.This publication has 65 references indexed in Scilit:
- Drugs of abuse and human placentaLife Sciences, 2011
- Methadone: A Substrate and Mechanism-Based Inhibitor of CYP19 (Aromatase)Drug Metabolism and Disposition, 2010
- Pharmacokinetics of Metformin during PregnancyDrug Metabolism and Disposition, 2010
- Opiates inhibit paclitaxel uptake by P-glycoprotein in preparations of human placental inside-out vesiclesBiochemical Pharmacology, 2009
- Drug transporters in the human blood-placental barrierBritish Journal of Pharmacology, 2009
- Simultaneous PET Imaging of P-Glycoprotein Inhibition in Multiple Tissues in the Pregnant Nonhuman PrimateJournal of Nuclear Medicine, 2009
- Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion ModelObstetrics and Gynecology International, 2009
- Inhibition of placental P‐glycoprotein: impact on indinavir transfer to the foetusBritish Journal of Clinical Pharmacology, 2007
- Pregnancy-Induced Changes in PharmacokineticsClinical Pharmacokinetics, 2005
- Drug Transfer and Metabolism by the Human PlacentaClinical Pharmacokinetics, 2004