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Compelling Relationship of CYP3A Induction to Levels of the Putative Biomarker 4beta-Hydroxycholesterol and Changes in Midazolam Exposure

Mangold, James and Wu, Fan and Rebello, Sam (2016) Compelling Relationship of CYP3A Induction to Levels of the Putative Biomarker 4beta-Hydroxycholesterol and Changes in Midazolam Exposure. Clinical Pharmacology in Drug Development, 5 (4). pp. 245-249. ISSN 2160-7648

Abstract

No abstract is required for this type of manuscript. But the following describes the overall intent of this work.
This is a commentary manuscript for your consideration for publication. This work describes our observations of a compelling relationship between the increase in the putative CYP3A plasma biomarker, 4-beta-hydroxycholesterol (4BHC), and the corresponding decrease in midazolam exposure (a sensitive CYP3A substrate) as a result of clinical CYP3A induction by rifampicin (RIF), including dose-response aspects. The results discussed include those from the literature and our own internal data. To our knowledge, this composite view (which we term an “Emax-Imax” model) has not been explicitly described by others. It is our hope that other researchers will elaborate on this observation/model and thereby help to better define the use of 4HC in the study of clinical variability and DDI.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] ST - Compelling Relationship of CYP3A Induction to Levels of the Putative Biomarker 4beta-Hydroxycholesterol and Changes in Midazolam Exposure [Field not mapped to EPrints] AU - Mangold, J. B. [Field not mapped to EPrints] AU - Wu, F. [Field not mapped to EPrints] AU - Rebello, S. [Field not mapped to EPrints] J2 - Clin [Field not mapped to EPrints] AD - Mangold,James B. Drug Metabolism and Pharmacokinetics, Novartis Institutes for Biomedical Research, East Hanover, NJ, USA. [Field not mapped to EPrints] DB - MEDLINE [Field not mapped to EPrints] DP - Ovid Technologies [Field not mapped to EPrints] AN - 27138133 [Field not mapped to EPrints]
Date Deposited: 05 Jan 2017 00:45
Last Modified: 05 Jan 2017 00:45
URI: https://oak.novartis.com/id/eprint/28117

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