Altered drug metabolism during pregnancy: hormonal regulation of drug-metabolizing enzymes

Importance of the field: Medication use during pregnancy is prevalent, but pharmacokinetic information of most drugs used during pregnancy is lacking in spite of known effects of pregnancy on drug disposition. Accurate pharmacokinetic information is essential for optimal drug therapy in mother and fetus. Thus, understanding how pregnancy influences drug disposition is important for better prediction of pharmacokinetic changes of drugs in pregnant women. Areas covered in this review: Pregnancy is known to affect hepatic drug metabolism, but the underlying mechanisms remain unknown. Physiological changes accompanying pregnancy are probably responsible for the reported alteration in drug metabolism during pregnancy. These include elevated concentrations of various hormones such as estrogen, progesterone, placental growth hormones and prolactin. This review covers how these hormones influence expression of drug-metabolizing enzymes (DMEs), thus potentially responsible for altered drug metabolism during pregnancy. What the reader will gain: The reader will gain a greater understanding of the altered drug metabolism in pregnant women and the regulatory effects of pregnancy hormones on expression of DMEs. Take home message: In-depth studies in hormonal regulatory mechanisms as well as confirmatory studies in pregnant women are warranted for systematic understanding and prediction of the changes in hepatic drug metabolism during pregnancy.