Quinney, Sara K.Benjamin, Tara D.Zheng, XiaomeiPatil, Avinash2019-05-152019-05-152017-10Quinney, S. K., Benjamin, T., Zheng, X., & Patil, A. S. (2017). Characterization of Maternal and Fetal CYP3A-Mediated Progesterone Metabolism. Fetal and pediatric pathology, 36(5), 400–411. doi:10.1080/15513815.2017.1354411https://hdl.handle.net/1805/19300INTRODUCTION: Progesterone is critical for maintaining pregnancy and onset of labor. We evaluated CYP450-mediated progesterone meta-bolism, specifically the contribution of CYP3A isoforms. MATERIALS AND METHODS: In vitro progesterone metabolism was characterized in human liver microsomes (HLMs) with and without selective cytochrome P450 inhibitors and in recombinant CYP3A4, CYP3A5, and CYP3A7. 6β-hydroxyprogesterone (6β-OHP) and 16α-hydroxyprogesterone (16α-OHP) metabolites were quantified by HPLC/UV and fit to the Michaelis-Menten equation to determine Km and Vmax. The effect of CYP3A5 expression on progesterone clearance was determined by in vitro in vivo extrapolation. RESULTS: Ketoconazole inhibited formation of both 6β-OHP and 16α-OHP more than 95%. 6β-OHP and 16α-OHP were both produced by CYP3A4 (2.3 and 1.3 µL/min/pmol, respectively) to a greater extent than by CYP3A5 (0.09 and 0.003 µL/min/pmol) and CYP3A7 (0.004 and 0.003 µL/min/pmol). CONCLUSIONS: Maternal clearance of progesterone by hepatic CYP450's is driven primarily by CYP3A4, with limited contributions from CYP3A5 and CYP3A7.en-USPublisher PolicyProgesteroneMetabolismCytochrome P450FetalPharmacokineticsArticle