Metabolism of nifedipine by placental CYP19A1 and competitive inhibition by chlorpromazine

Patients with eclampsia are treated with antihypertensive drugs such as nifedipine and sedatives like chlorpromazine. The placenta, a unique organ connecting mother and baby, can regulate the intake and export of substances and mediate their metabolism. This report examined the metabolism of nifedipine in human placenta microsomes, with K_m and V_max values of 12.90 ± 1.01 μM and 39.33 ± 0.88 pmol/mg protein/min, respectively. Further research demonstrated that cytochrome P450 19A1 (CYP19A1) was the primary enzyme responsible for metabolizing nifedipine in the placenta, confirmed through selective inhibition, Jarrett (JAR) cell verification, recombinant enzyme identification, and metabolism correlation analysis using the CYP19A1-specific substrate androstenedione. Additionally, this study investigated the effect of chlorpromazine on nifedipine metabolism in the placenta. The results indicated that chlorpromazine competitively inhibited CYP19A1 activity in human placenta microsomes and CYP19A1 supersomes, thus decreasing nifedipine metabolism mediated by this enzyme. In brief, this study confirms that nifedipine is metabolized in the human placenta and can interact with chlorpromazine via CYP19A1-mediated pathways in in vitro conditions.