MEDCHEM/PCEUT 527 - Winter 2009
Advanced Drug Metabolism

Course Description

Considerations of the biochemical mechanisms for the biotransformation of drugs and foreign compounds. Includes reaction mechanisms, ultrastructural considerations, induction mechanisms, methodology, kinetics of inhibition and activation, steroid and amine metabolism. Course is offered jointly with PHCOL 527 on odd years.

Course Outline and Required Reading

Course Outline 2009 (DOC)

Articles and Chapters

Article for Dr. Thummel's class 2/14/07 - Cheung C, Yu A-M, Chen C-S, Krausz KW, Byrd LG, Feigenbaum L, Edwards RJ, Waxman DJ, and Gonzalez FJ, "Growth Hormone Determines Sexual Dimorphism of Hepatic Cytochrome P450 3A4 Expression in Transgenic Mice," Journal of Pharmacology and Experimental Therapeutics 2006; 316:1328­1334 (PDF)

Review - Krueger SK and Williams DE, "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism," Pharmacology & Therapeutics 2005; 106:357-387  (PDF)

Review - Kitamura S, Sugihara K and Ohta S , "Drug-Metabolizing Ability of Molybdenum Hydroxylases," Drug Metab. Pharmacokinet. 2006; 21:83-98  (PDF)

Article - Benedetti MS, Whomsley R and Baltes E, "Involvement of Enzymes Other than CYPs in the Oxidative Metabolism of Xenobiotics," Expert Opin. Drug Metab. Toxicol. 2006; 2: 895-921 (PDF)

Article - Guengerich FP, "Cytochrome P450s and Other Enzymes in Drug Metabolism and Toxicity," The AAPS Journal 2006; 8 (1) Article 12 (PDF)

Article - Johnson EF, "THE 2002 BERNARD B. BRODIE AWARD LECTURE - Deciphering Substrate Recognition by Drug-Metabolizing Cytochromes P450," Drug Metab Dispos 2003 31:1532-1540 (PDF)

Article - Nelson DR, Zeldin DC, Hoffman SMG, Maltais LJ, Wain HW and Nebert DW, "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants," Pharmacogenetics 2004 14:1-18 (PDF)

Article - Vasiliou V, Pappa A and Estey T, "Role of Human Aldehyde Dehydrogenases in Endobiotic and Xenobiotic Metabolism," Drug Metab Rev 2004 36:279-299 (PDF)  (Higher resolution figures-PDF)

Chapters from Drug Metabolizing Enzymes: Cytochrome P450 and Other Enzymes in Drug Discovery and Development, edited by JS Lee, RS Obach and MB Fisher, 2003:

• Chapter 2 - Mutlib AE and Schockcor JP - "Application of LC/MS, LC/NMR, NMR and Stable Isotopes in Identifying and Characterizing Metabolites" (PDF)
• Chapter 3 - Uetrecht J - "Bioactivation" (PDF)
• Chapter 14 - Lang D and Kalgutkar AS - Non-P450 Mediated Oxidative Metabolism of Xenobiotics" (PDF)

Article - Morisseau C and Hammock BD, "Epoxide Hydrolases: Mechanisms, Inhibitor Designs, and Biological Roles," Annu Rev Pharmacol Toxicol 2005 45:311­33 (PDF)

Chapter 12 from Handbook of Drug Metabolism - Rodrigues AD, "Applications of Heterologous Expressed and Purified Human Drug Metabolizing Enzymes: An Industrial Perspective," Section III Methodology (PDF)