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Talk: General factors affecting drug metabolism: the role ... (38 min)

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DETAILED SLIDE INDEX

  1. 1. Nuclear receptor (NR) superfamily
  2. 2. Content of presentation
  3. 3. Detoxication function
  4. 4. Gene transcription
  5. 5. Regulation of gene expression
  6. 6. Signaling pathways
  7. 7. NR-mediated gene activation
  8. 8. NRs in drug metabolism induction
  9. 9. Xenobiotic/drug metabolism
  10. 10. AhR - general
  11. 11. AhR signal transduction
  12. 12. PXR - general
  13. 13. PXR - signal transduction
  14. 14. hPXR LBD x-ray structure
  15. 15. CAR - general
  16. 16. CAR - signal transduction
  17. 17. hCAR/PXR LBD x-ray structure
  18. 18. CAR/PXR - ligands/activators
  19. 19. CAR/PXR - target genes
  20. 20. CYP3A4 promoter organization
  21. 21. Drug metabolism induction
  22. 22. CAR/PXR - knockout animals
  23. 23. Induction - species-specificity
  24. 24. Induction - variability in man (1)
  25. 25. Induction - variability in man (2)
  26. 26. P450s and CAR/PXR redundancies
  27. 27. Drug metab. induction - examples
  28. 28. Preparation of human hepatocytes
  29. 29. CYP mRNAs induction in hepatoc.
  30. 30. CYP proteins induction in hepatoc.
  31. 31. CYP activity induction in hepatoc.
  32. 32. Conclusion

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TALK'S CITATION

Maurel, P. (2007), "General factors affecting drug metabolism: the role of nuclear receptor superfamily members in induction", in Daly, A. (ed.), Drug Metabolizing Enzymes: Fundamentals, Study Methods, Recent Advances and Clinical Significance, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/?t=BL0091097)

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ABOUT THIS TALK

Speaker(s)

Dr. Patrick Maurel Show Biography

SPEAKER BIOGRAPHY

Dr. Patrick Maurel – INSERM, France

Patrick Maurel graduated from Montpellier University and received his PhD in Biochemistry from the University of Paris VII in 1976. In 1983-84, he was an International Research Fellow of the US Department of Health and Human Services in Richmond VA. He joined Inserm (Institut National de la Sante et de la Recherche Medicale) in 1976 and is now Research Director and head of Inserm Unit U632 "Hepatic Physiopathology" in Montpellier. His current research interests include detoxication, hepatitis C virus, liver stem cells.

Publication Date

October, 2007

Topics Covered

Drug metabolism and gene transcription... more

TOPICS COVERED IN THIS TALK

  • Drug metabolism and gene transcription
  • Role of nuclear receptors in drug metabolism induction
  • Aryl hydrocarbon receptor
  • Pregnane X receptor
  • Constitutive androstane receptor
  • Human examples of drug metabolism induction

Series

Drug Metabolizing Enzymes

OTHER TALKS IN THIS SERIES

INTRODUCTION
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Prof. Ann Daly

TOPICS COVERED IN THIS TALK

  • Genes and gene products
  • Role of CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1 in drug metabolism
  • Regulation of gene expression
  • Effect of genetic variation
  • Clinically relevant polymorphisms
Play '2. Introduction to drug metabolism enzymes'
2. Introduction to drug metabolism enzymes More info
Dr. Dennis Smith

TOPICS COVERED IN THIS TALK

  • Metabolism of lipophilic molecules
  • Phase I and Phase II enzymes
  • Location
  • Mechanism
  • Typical substrates
  • Genetic variation
  • Species variation
  • Inhibition and drug interactions
  • Drug design
GENERAL FACTORS AFFECTING DRUG METABOLISM
Now Playing
3. General factors affecting drug metabolism: the role of nuclear receptor superfamily members in induction
Dr. Patrick Maurel
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4. Effect of physiological factors and disease on drug metabolism More info
Prof. Edward Morgan

TOPICS COVERED IN THIS TALK

  • Effect of physiological and pathophysiological conditions on drug metabolizing enzymes (DMEs)
  • Role of growth hormones and transcription factors in sex-dependent expression
  • Drug clearance and age
  • Developmental regulation
  • Impact of infection and inflammatory disease on DME expression
  • Clinical consequences
Play '5. Drug metabolism and liver disease'
5. Drug metabolism and liver disease More info
Prof. Robert Branch

TOPICS COVERED IN THIS TALK

  • Liver disease and drug clearance
  • Mechanistic explanations
  • Intact hepatocyte hypothesis
  • Sick cell theory
  • Sequential progressive model of liver disease
  • Viral liver disease
  • Alcoholic liver disease
  • Hepatocellular carcinoma
  • Liver transplantation
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6. Laboratory methods for the in vitro study of drug metabolism More info
Dr. Charles Crespi

TOPICS COVERED IN THIS TALK

  • Major classes of DMEs
  • Systems for laboratory study
  • Practical aspects
  • Examples of application
  • Obtaining high quality data
  • Minimizing artefacts
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7. Prediction of pathways of drug metabolism More info
Dr. Maurice Dickins

TOPICS COVERED IN THIS TALK

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PHASE I METABOLIZING ENZYMES: CYTOCHROME P450S
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8. Crystal structures of drug-metabolizing P450 monooxygenases More info
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TOPICS COVERED IN THIS TALK

  • Introduction to CYP450 architecture
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  • Redox partner interactions
  • Membrane topology
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Prof. Gordon Roberts

TOPICS COVERED IN THIS TALK

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TOPICS COVERED IN THIS TALK

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  • Gene expression
  • Molecular mechanisms of regulation
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  • Polymorphic variation
  • Inter-individual variation
  • Drug-drug interactions
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13. Pharmacogenetics of the P450s More info
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TOPICS COVERED IN THIS TALK

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Res. Prof. Clement Furlong

TOPICS COVERED IN THIS TALK

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  • PON1 status as a risk factor in carotid artery disease
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Play '16. Glucuronidation and the UDP - glucuronosyltransferases'
16. Glucuronidation and the UDP - glucuronosyltransferases More info
Prof. Peter Mackenzie
Prof. John Miners

TOPICS COVERED IN THIS TALK

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TOPICS COVERED IN THIS TALK

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TOPICS COVERED IN THIS TALK

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TOPICS COVERED IN THIS TALK

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  • Implications for rational drug design
CLINICAL ASPECTS
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TOPICS COVERED IN THIS TALK

  • Metabolic drug interactions
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Play '23. Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism: psychopharmacology and pain'
23. Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism: psychopharmacology and pain More info
Prof. Julia Stingl (formerly Kirchheiner)

TOPICS COVERED IN THIS TALK

  • Pharmacogenetic polymorphisms
  • Biotransformation and clinical outcome
  • Consequences of genotyping
  • Feasibility for genotyping in antidepressant drug treatment
  • Polymorphic cytochrome P450 enzyme CYP2D6
  • Feasibility for genotyping in pain treatment
  • CYP2C9, CYP2D6 and nonsteroidal analgetic drugs
Play '24. Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism: internal medicine'
24. Clinical importance of pharmacogenetic polymorphisms affecting drug metabolism: internal medicine More info
Prof. Julia Stingl (formerly Kirchheiner)

TOPICS COVERED IN THIS TALK

  • Cardiovascular drugs and genetic polymorphisms
  • Antihypertensive drug treatment
  • Feasibility for genotyping
  • Cancer treatment and genetic polymorphisms
  • Potential for pharmacogenetic diagnostics
  • Thiopurine-methyl-transferase (TPMT)
  • Dihydropyrimidine dehydrogenase
  • Efficacy of antiemetic treatment
  • Future clinical study directions in pharmacogenetics
LATEST UPDATES IN THE FIELD
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25. Mammalian flavin-containing monooxygenases More info
Prof. Allan Rettie

TOPICS COVERED IN THIS TALK

  • Flavin-containing monooxygenases (FMOs)
  • FMO structure, function and regulation
  • Role of FMOs drug metabolism and drug toxicity
  • Methods for distinguishing between FMO and P450 catalysis

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