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PMID: 12605548 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Predicting inductive drug-drug interactions.

Pharmacogenomics ·Vol. 4 ·No. 2 ·2003-03-00 ·Pages 141-52

Liddle C, Robertson GR

Abstract

Until recently, inductive drug-drug interactions have proved difficult to predict prior to formal pharmacokinetic studies in man. Even then, important interactions have often gone unrecognized until clinical sequelae have occurred in the postmarketing phase. Recent advances in the molecular and cellular biology of nuclear receptors have revealed that there are 'sensors' for xenobiotics, which in turn transactivate genes involved in drug metabolism and excretion. Knowledge of these mechanisms has allowed the development of assay systems that detect the potential of drugs to cause gene induction, well before human studies are contemplated.

MeSH Terms
Animals Cell Line Cell-Free System Constitutive Androstane Receptor Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System/genetics,metabolism Drug Interactions/genetics Humans Mice Mice, Transgenic Models, Animal Pregnane X Receptor Receptors, Cytoplasmic and Nuclear/physiology Receptors, Steroid/physiology Response Elements Transcription Factors/physiology Xenobiotics/adverse effects,metabolism,pharmacokinetics
Chemicals
Constitutive Androstane Receptor Pregnane X Receptor Receptors, Cytoplasmic and Nuclear Receptors, Steroid Transcription Factors Xenobiotics Cytochrome P-450 Enzyme System CYP3A protein, human Cytochrome P-450 CYP3A
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Liddle Christopher
Department of Clinical Pharmacology, Storr Liver Unit, Westmead Millennium Institute and University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia. chris_liddle@wmi.usyd.edu.au
Robertson Graham R
Article Info
Journal
Pharmacogenomics
Abbr.
Pharmacogenomics
ISSN
1462-2416
Published
2003-03-00
Pages
141-52
Language
English
Region
England
NLM ID
100897350
Subset
IM
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