Assessment of induced CYP3A activity in pregnant women using 4 beta-hydroxycholesterol: Cholesterol ratio as an appropriate metabolic marker

Aims: This study was aimed at evaluating changes in CYP3A activity following and during pregnancy by analyzing metabolic markers for CYP3A activity, which can help avoid unnecessary drug exposure and invasive sampling. Methods: Forty-eight pregnant women and 25 non-pregnant women were enrolled in this study. Plasma and urine samples were collected from the pregnant women during each trimester and from the nonpregnant women for evaluation of metabolic markers for CYP3A activity. Metabolic markers for CYP3A activity were measured using GC-MS. Results: An increased 4 beta-hydroxycholesterol/cholesterol ratio, consistent with high CYP3A activity, was observed in pregnant women compared with that in non-pregnant women; however, no differences were observed among trimesters. No significant differences were observed in urinary markers. Conclusions: We observed an increase in the activity of CYP3A following but not during pregnancy when measured using the 4 beta-hydroxycholesterol/cholesterol ratio. In addition, based on our results, we suggest that the plasma 4 beta-hydroxycholesterol/cholesterol ratio be used to measure CYP3A activity in pregnant women. (c) 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.