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Updated: May 20, 2026
Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures
Published on: March 28, 2017
Methods for the quantitative evaluation and prediction of CYP enzyme induction using human in vitro systems
Masashi Honma1, Masanari Kozawa, Hiroshi Suzuki
1The University of Tokyo Hospital, Faculty of Medicine, Department of Pharmacy, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan +81 3 3815 5411 ; +81 3 3816 6159 ; mhonma-tky@umin.ac.jp.
Importance Of The Field:
For successful drug development, it is important to investigate the potency of candidate drugs causing drug-drug interactions (DDI) during the early stages of development. The most common mechanisms of DDIs are the inhibition and induction of CYP enzymes. Therefore, it is important to develop co.mpounds with lower potencies for CYP enzyme induction.
Areas Covered In This Review:
The aim of the present paper is to present an overview of the current knowledge of CYP induction mechanisms, particularly focusing on the transcriptional gene activation mediated by pregnane X receptor, aryl hydrocarbon receptor and constitutive androstane receptor. The adoptable options of in vitro assay methods for evaluating CYP induction are also summarized. Finally, we introduce a method for the quantitative prediction of CYP3A4 induction considering the turnover of CYP3A4 mRNA and protein in hepatocytes based on the data obtained from a reporter gene assay.
What The Reader Will Gain:
In order to predict in vivo CYP enzyme induction quantitatively based on in vitro information, an understanding of the physiological induction mechanisms and the features of each in vitro assay system is essential. We also present the estimation method of in vivo CYP induction potency of each compound based on the in vitro data which are routinely obtained but not necessarily utilized maximally in pharmaceutical companies.
Take Home Message:
It is desirable to select compounds with lower potencies for the inductive effect. For this purpose, an accurate prioritization procedure to evaluate the induction potency of each compound in a quantitative manner considering the pharmacologically effective concentration of each compound is necessary.
