Influence of Changes in Physiology, Transporters, and Enzyme Expression on Disposition and Metabolism of Drugs during Pregnancy and Clinical Implications

摘要: Safe and effective administration of drugs during pregnancy is a challenge due to physiological changes in the mother limited development mechanisms metabolism xenobiotics fetus. In particular, concentrations transporters such as PgP, BCRP, MRP3, OCT3, OCTN1 change mother's placenta fetal tissues with advancing gestation, confounding standard therapies. Drug-metabolizing enzymes developing fetus differ from those liver mother. For example, CYP3A7 predominant CYP3A isoform fetus, while CYP3A4 adults. These isoforms have different substrates kinetics, thus, challenges can be very different. Hence, there need for selectivity titrating dose maintain efficacy and/or minimize side effects pregnancy. This particularly important narrow therapeutic window or marked pharmacologic toxicological outcomes, also that are metabolized predominantly by single enzyme transporter. Before initiating any new drug regimen pregnancy, systemic monitoring plasma exposure, especially initial days therapy. It anticipated advancement understanding transport potential making early predictions respect effect tolerance may possible, resulting safer therapies both pregnant mothers fetus. Keywords: pregnancy; fetus; placenta; drug metabolism; transport