This career development award is being sought by a doctoral-level clinical pharmacist nearing the completion of his PhD in Epidemiology who is fully committed to a career as an independent, federally-funded academic investigator in the pharmacoepidemiology of aging. The Candidate will use the proven """"""""80% research / 20% clinical"""""""" career model, which will provide a source of clinical research questions as well as the infrastructure to conduct patient-oriented research. A three-phase career development plan has been formulated specifically to address gaps in the Candidate's background. In addition to the research project that will serve as the """"""""core curriculum,"""""""" the career development plan will further develop his focus on aging, and provide classroom and laboratory training in molecular and genetic epidemiology with the objective of enabling him to collaborative knowledgeably and effectively with laboratory scientists. In the latter phase of the award, the Candidate will develop additional research ideas, perform pilot studies, and apply for federal research (e.g., R01) funding. A formal career advisory process is an integral component of the career development plan. The research component of this proposal is a study of risk factors for severe neurologic phenytoin toxicity, which has been shown in multiple data sources to be one of the leading causes of serious adverse drug reactions, particularly in the elderly. The study will examine therapy- and patient-specific factors, including age and polymorphisms in the genes that express cytochrome P450 enzyme isoforms CYP2C19 and CYP2C9, which are responsible for phenytoin metabolism. The study design is a case-control study that is nested within the population of patients seen for seizure disorders within our health system. Concurrent surveillance in the three major hospitals in our health system will be used to identify potential cases, with controls being randomly selected from patients prescribed phenytoin for seizure disorders within our health system. This career development award will enable the Candidate to complete the development of the skills and experience that he will need to evolve into an independent academic investigator in the pharmacoepidemiology of aging.
