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Drug Metab Pharmacokinet. 2018 Jun;33(3):173-178. doi: 10.1016/j.dmpk.2018.04.004. Epub 2018 Apr 25.

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

Author information

1
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
2
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; Kidney Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea.
3
Department of Obstetrics and Gynecology, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
4
Department of Obstetrics and Gynecology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea.
5
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea. Electronic address: joocho@snu.ac.kr.

Abstract

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 non-pregnant women for evaluation of metabolic markers for CYP3A activity. Metabolic markers for CYP3A activity were measured using GC-MS.

RESULTS:

An increased 4β-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 4β-hydroxycholesterol/cholesterol ratio. In addition, based on our results, we suggest that the plasma 4β-hydroxycholesterol/cholesterol ratio be used to measure CYP3A activity in pregnant women.

KEYWORDS:

4β-hydroxycholesterol/cholesterol; Cytochrome P450 3A; GC-MS; Metabolic markers; Pregnancy

PMID:
29759884
DOI:
10.1016/j.dmpk.2018.04.004
[Indexed for MEDLINE]

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