2007,个体化用药 - 高血压治疗的未来展望,药物基因组学.ppt

Pharmacogenomics:The Promise of Personalized Medicine  Christina Aquilante, Pharm.D. Assistant Professor Department of Pharmaceutical Sciences School of Pharmacy University of Colorado at Denver and Health Sciences Center Objectives Provide an overview of pharmacogenomics and its clinical relevance Discuss clinically-relevant examples of: Drug metabolism pharmacogenomics Drug target pharmacogenomics Discuss the challenges facing pharmacogenomic studies and the movement of pharmacogenomics into clinical practice Discuss pharmacogenomics from the FDA and pharmaceutical industry perspective Interindividual Variability in Drug Response Disease Drug Class Rate of Poor Response Asthma Beta-agonists 40-75% Hypertension Various 30% Solid Cancers Various 70% Depression SSRIs, tricyclics 20-40% Diabetes Sulfonylureas, others 50% Arthritis NSAIDs, COX-2 inhibitors 30-60% Schizophrenia Various 25-75% Factors Contributing to Interindividual Variability in Drug Disposition and Action Age Race/ethnicity Weight Gender Concomitant Diseases Concomitant Drugs Social factors GENETICS Human Genome Project Determine the sequence of the 3 billion nucleotides that make up human DNA Characterize variability in the genome Identify all the genes in human DNA The Era of Genomic Medicine: Improve prediction of drug efficacy or toxicity Improve the diagnosis of disease Earlier detection of genetic predisposition to disease Genetics or Genomics? Pharmacogenetics Study of how genetic differences in a SINGLE gene influence variability in drug response (i.e., efficacy and toxicity) Pharmacogenomics Study of how genetic (genome) differences in MULTIPLE genes influence variability in drug response (i.e., efficacy and toxicity) Current Concept of Pharmacogenomics Potential of Pharmacogenomics Clinical Relevance Can we predict who will derive an optimal response? Can we predict who will have a toxicity? Host (patient) genotype determines optimal drug therapy approach Disease