Distribution of Exogenous and Endogenous CYP3A Markers and Related Factors in Healthy Males and Females

The AAPS Journal
Jieon LeeJoo-Youn Cho

Abstract

Cytochrome P450 (CYP) 3A is an important drug-metabolizing enzyme in humans. Assessing CYP3A activity is necessary for predicting therapeutic outcomes or the potential adverse events of various therapeutics. This study sought to evaluate the distribution of endogenous and exogenous markers reflecting hepatic CYP3A activity and related factors affecting its activity in healthy male and female. Each subject was given a single 1 mg dose of midazolam intravenously. Pharmacokinetics, pharmacometabolomics, and pharmacogenomics analyses were performed to evaluate CYP3A activity. Urinary and plasma steroids were quantified with gas chromatography coupled with triple-quadrupole mass spectrometry (GC-MS), and the concentrations of midazolam and its metabolites were quantified with liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). A total of 100 subjects completed this study. Midazolam clearance (MDZ CL) and the metabolic ratio (MDZ MR) were significantly correlated with 6β-OH-cortisol/cortisol and 6β-OH-cortisone/cortisone. MDZ CL, 6β-OH-cortisol/cortisol, and 6β-OH-cortisone/cortisone decreased with increasing age (Pearson r = -0.333, -0.329, and -0.528, respectively; P < 0.05). When the markers were c...Continue Reading

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Citations

May 28, 2019·Clinical Pharmacokinetics·Gaëlle MaglioccoYoussef Daali
Jan 1, 2019·Journal of Korean Medical Science·Andrew HyoungJin KimJoo-Youn Cho
Dec 22, 2020·Drug Metabolism and Pharmacokinetics·Soyoung LeeJoo-Youn Cho
Nov 8, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Priska KaufmannJasper Dingemanse
Jun 15, 2021·Frontiers in Cellular and Infection Microbiology·Andrew HyoungJin KimJoo-Youn Cho

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Methods Mentioned

BETA
genotyping
PCR

Clinical Trials Mentioned

NCT02579434

Software Mentioned

7500 Real - Time PCR System
SPSS
Phoenix WinNolin
SAS

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