100% course work in the form of two written research assignments in topics chosen by the Module leaders to meet the learning outcomes of the module. An aggregate mark of 50% must be achieved in order to pass the module.

Module 1 and a working knowledge of biology in relation to genetics.

The aims of the module are to provide the student with the basic concepts of pharmacogenomics and the importance of these concepts to the drug discovery and development process in relation to adverse drug events, biomarkers of disease susceptibility and the individualisation of medicine in the clinical setting now and in the future.

By the end of the module students will be able to:

·        Understand the principles of pharmacogenomics

·        Appreciate the role of pharmacogenomics to the drug discovery and development process

·        Understand the central role that CYP2D6 plays in drug biotransformations and the clinical consequences of the genetic polymorphisms in this enzyme

·        Understand the role that the CYP2C subfamily has in drug biotransformations and the clinical consequences of the genetic polymorphisms in these enzymes

·        Understanding the central role that TPMT plays in the clinical outcomes of individuals undergoing therapy with 6-mercaptopurine or azathioprine drugs with respect to adverse drug reactions and failure of efficacy.

·        Appreciate the complex role that pharmacogenomics plays in adverse drug reactions.

·        Understanding of the role that drug transporter systems with respect to drug disposition and toxicity

·        Ability to interpret and integrate pharmacogenomics information

·        Gained problem solving abilities in relation to pharmacogenomics

·        Be able to apply these skills in the assessment of actual and potential adverse drug reactions

Definition of terms.

 ·        Pharmacogenomics in relation to genotype, phenotype, SNPs, haplotypes, biochemistry and molecular biology.

 ·        Major cytochrome P450 biotransformation enzymes known to have clinical relevant pharmacogenomics variation in relation to adverse drug reactions, CYP2D6, CYP2C9, CYP2C19.

 ·        Major conjugating P450 biotransformation enzymes known to have clinical relevant pharmacogenomics variation in relation to adverse drug reactions, TPMT, NAT2, UGT1A1.

 ·        Role of drug transporters in drug disposition and adverse drug reactions.

 ·        Pharmacogenomic biomarkers of disease susceptibilities (drug metabolism enzymes, transporters, receptors) as future potential drug development candidates.

 ·        The role of pharmacogenomics in clinical trials.

 ·        Population ethnic pharmacogenomic variations and the implication for the pharmaceutical industry.

 ·        The use of pharmacogenomics in preclinical development to predict potential adverse drug reactions in the clinical development phase of new chemical entities (NCEs).

 ·        What role do the regulatory agencies see for pharmacogenomics now and in the future.

  ·        Future perspectives for pharmacogenomics in personalised medicines.

 

A balance of lectures, case studies and group workshops delivered by members of the University of Surrey, other academic institutions and invited external experts usually consultants or working in the regulatory or pharmaceutical industry.

Pre-course web-based research. Printed notes and references will support this module where necessary. Further recommended reading includes:

Pharmacogenomics and Personalised Medicine, 2008 (Ed. Cohen, N.), Humana Press, New York, . ISBN 978-1-934115-04-6.

Pharmacogenomics data base: http://www.pharmgkb.org

CYP alleles data base: http://www.cypalleles.ki.se

NAT alleles data base: http://louisville.edu/medschool/pharmacology/consensus-human-arylamine-n-acetyltransferase-gene-nomenclature

Ingelman-Sundberg, M, Sim, S C. (2010). Pharmacogenetic biomarkers as tools for improved drug therapy; emphasis on the cytochrome P450 system. Biochem. Biophys. Res. Comm., 396, 90–94.

Kirchheiner, J, Seeringer, A. (2007). Clinical implications of pharmacogenetics of cytochrome P450 drug metabolizing enzymes. Biochim. Biophys. Acta, 1770, 489–494.

Limdi, N A, Arnett, D K, Goldstein, J A, Beasley T M, McGwin, G, Adler, B K,

Acton, R T. (2008). Influence of CYP2C9 and VKORC1 on warfarin dose,

anticoagulation attainment and maintenance among European, American and African Americans. Pharmacogenomics,  9, 511–526.

Marsh, S, Hoskins, J M. (2010). Irinotecan Pharmacogenomics. Pharmacogenomics, 11, 1003–1010.

Rosemary, J, Adithan, C. (2008). The Pharmacogenetics of CYP2C9 and CYP2C19: Ethnic Variation and Clinical Significance. Curr. Clin. Pharmacol., 2, 93-109.

Yee, S W, Chen, L, Giacomini, K M. (2010). Pharmacogenomics of membrane transporters: past, present and future. Pharmacogenomics , 11, 475–479