WVU Health Sciences Center School of Pharmacy

West Virginia University - School of Pharmacy
Drug Metabolism - PHAR 781
Spring 2007 (3 cr. hr)

Course Coordinator:

Grazyna Szklarz, 2035A HSCN, 293-1473, gszklarz@hsc.wvu.edu

Other Faculty:

Patrick Callery, 2028 HSCN, 293-1482, pcallery@hsc.wvu.edu
Robert Griffith, 2026 HSCN, 293-1481,rgriffith@hsc.wvu.edu
David Lalka, 2040 HSCN, 293-1475 dlalka@hsc.wvu.edu
Joseph Ma, G126 HSCN, 293-1449, jma@hsc.wvu.edu

Class times: Lecture: two 1.5 hr. per week , TBA

Required Text

N/A

Suggested Textbooks:

General:

1.	Gibson, G.G. and Skett, P."Introduction to Drug Metabolism ", 3rd edition, Nelson Thornes Publ., Cheltenham, U.K., 2001.
2.	"Handbook of Drug Metabolism", Woolf, T.F., ed., Marcel Dekker, New York, Basel, 1999.
3.	"Metabolic Drug Interactions ", Levy, R.H., Thummel, K.E., Trager, W.F., Hansten, P.D., Eichelbaum, M., eds., Lippincott, Williams & Wilkins, Philadelphia, 2000.
4.	"Principles of Drug Action. The basis of Pharmacology ", Pratt, W.B., Taylor, P., eds., 3rd edition, Churchill Livingstone, New York, 1990. (Chapter 3, also others, especially Chapters 1, 5, 6, 7).
5.	"Foye’s Principles of Medicinal Chemistry ", Williams, D.A., Lemke, T.L., eds., 5th edition, Lippincott Williams & Wilkins, Philadelphia, 2002.
6.	Silverman, R.B. "The Organic Chemistry of Drug Design and Drug Action ", Academic Press, San Diego, 1992.
7.	"Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry ", Block, J.H., Beale, J.M., eds., 11th edition, Lippincott Williams & Wilkins, Philadelphia, 2004.

Proteins:

1.	Creighton, T.E., "Proteins. Structures and Molecular Properties ", 2nd edition, W.H. Freeman and Company, New York, 1993.
2.	Fersht, A., "Structure and Mechanism in Protein Science. A Guide to Enzyme Catalysis and Protein Folding ", W.H. Freeman and Company, New York, 1999.

Drug-metabolizing enzymes:

1.	"Cytochrome P450. Structure, Mechanism and Biochemistry ", Ortiz de Montellano, P.R., ed., 3rd edition, Kluwer Academic/Plenum Press, New York, 2005.
2.	"Enzyme Systems that Metabolise Drugs and Other Xenobiotics ", Ioannides, C., ed., John Wiley and Sons, Ltd., Chichester, U.K., 2002.
3.	Lewis, D.F.V., "Guide to Cytochromes P450 Structure and Function " Taylor and Francis, London, New York, 2001.

Other Required Items

N/A

Catalog Description

This course presents a comprehensive view of the field of drug metabolism with an emphasis on chemistry and enzymology of drug biotransformation pathways, and current methods in drug metabolism research.

Course Overview

This course covers three major areas of the drug metabolism field, such as chemistry of metabolic reactions, enzymology of drug metabolizing enzymes, and methods used in drug metabolism studies.
The chemistry section covers such topics as the chemistry of phase I and II reactions, and stereochemistry of drug metabolism. The enzymology section includes enzyme catalysis, inhibition and inactivation, as well as detailed discussion on structure and mechanism of drug metabolizing enzyme, such as cytochromes P450, FMOs, conjugating enzymes, etc. The methods section covers current techniques for studying drug metabolism and in vitro-in vivo predictions.
The course is taught as a lecture/discussion, with required student presentations on a topic in the area of in vitro models of drug metabolism.

Educational Outcomes

1.	Understand chemical processes involved in biotransformation of drugs.
2.	Obtain the necessary background in the principles of enzymatic catalysis and ligand binding, enzyme kinetics, and enzyme inhibition and inactivation.
3.	Understand the role and various mechanisms of drug metabolizing enzymes.
4.	Know the principles and applications of different techniques for studying drug metabolism.

Ability-Based Outcomes

1.	Predict metabolic reactions in phases I and II of drug biotransformation pathways.
2.	Describe the importance of stereochemistry in drug metabolism.
3.	Contrast and compare various mechanisms for enzyme catalysis, kinetics and ligand binding.
4.	Describe the mechanisms and importance of enzyme inhibition, inactivation and induction in drug metabolism.
5.	Describe the structure, mechanism and function of various drug metabolizing enzymes.
6.	Evaluate the importance of pharmacogenetics to drug metabolism.
7.	Contrast and compare different techniques used in drug metabolism studies.

Examination and Grading Policies

Evaluation

All three exams are open-book take home exams, to be completed within one week. No final exam will be given.

Exam I	30 pts
Exam II	30 pts
Exam III	30 pts
Student presentation	10 pts
Total	100 pts

Course Grades

Grading will be based on the total points earned on the examinations listed above as follows:

A	(90-100%)
B	(80-89.9%)
C	(70-79.9%)
D	(60-69.9%)
F	(<60%)

Student Responsibilities and Attendance

Regular attendance at lectures is expected although roll will not be taken. Students who miss lectures are responsible for getting the material and any announcements from a classmate. Each student is required to give one oral presentation on an assigned topic. With respect to exams, students are responsible for all textbook and other material assigned and for lecture material covered. Plagiarism will not be tolerated. Makeup exams will be given only if the student has a bona fide medical excuse or other legitimate reason beyond the student =s control. Time and type of makeup exam will be at the convenience of the instructor.

Course Outline

Lecture Topics:

I	Introduction	(2)
	- organizational meeting
	-drug absorption, distribution and excretion

II.	Drug biotransformation pathways:	(3)
	A. Phase I reactions
	B. Phase II reactions

III.	Stereochemical aspects of drug metabolism	(1)

IV.	Enzymes:	(3)
	A. Enzyme kinetics
	B. Mechanism of enzymatic catalysis and ligand binding
	C. Enzyme inhibition and inactivation

Written exam I

V.	Drug metabolizing enzymes:
	A. Cytochromes P450	(4)
	– structure and catalytic cycle
	– reactions catalyzed
	– isoforms and substrate specificity
	B. Other oxidative enzymes:	(2)
	– FMOs
	– other oxidative enzymes
	C. Conjugation enzymes	(1)
	D. Proteases	(1)
	E. Other enzymes	(1)

Written Exam II

VI.

Enzyme induction

(1)

VII.

Pharmacogenetics

(1)

VIII.	Alteration of pulmonary phase I and phase II	(1)
	enzymes by particulate matters.

IX.

TBA– guest lectures

(2)

X.	In vitro models of drug metabolism	(2)
	- student presentations

XI.	Techniques for studying drug metabolism:
	A. Analytical methods and isotope application	(2)
	B. In vitro studies:	(1)
	– heterologous expression
	C. In vivo metabolism studies	(1)

XII.

In vitro-in vivo predictions

(1)

Written Exam III

Social Justice Statement

West Virginia University is committee to social justice. We concur with that commitment and will foster a nurturing learning environment based upon open communication, mutual respect, and non-discrimination. Our University does not discriminate on the basis of race, sex, age, disability, veteran status, religion, sexual orientation, color or national origin. Any suggestions as to how to further such a positive and open environment in this class will be appreciated and given serious consideration. If you are a person with a disability and anticipate needing any type of accommodation in order to participate in this class, please advise us and make appropriate arrangements with Disability Services at 293-6700.