Abstract

CHANGES IN HEPATIC DRUG METABOLIZING ENZYMES DURING PREGNANCY

Sanaa Taha Abdulateef* and Dhameer Saleh Saeed

Abstract

Sweeping physiological and biochemical changes occur during pregnancy, and the pharmacokinetics of many drugs are altered over the course of gestation. Small clinical studies suggest that the activity of many of the drug metabolizing enzymes is altered during pregnancy. For example, CYP1A2 activity decreases during pregnancy while CYP2D6 activity increases during pregnancy. As more than half of all women require prescription drugs at some point during pregnancy, it is vital to understand how pregnancy affects the drug metabolizing enzymes. We propose that during pregnancy, circulating sex steroids, vitamins and cytokines act directly on hepatocytes to up- and down-regulate drug metabolizing enzymes through transcriptional mechanisms leading to altered enzyme synthesis. Furthermore, we propose that because pregnancy acts on enzyme expression, pharmacokinetic changes can be extrapolated from one substrate to another to predict pharmacokinetic changes during pregnancy.

Keywords: Hepatic drug metabolizing enzymes, pregnancy.