This proposal has been designed to provide a comprehensive training and research plan which will facilitate my long-term career goal of becoming an independent investigator in the area of clinical pharmacotherapy research. To accomplish this objective, three short-term goals have been developed: 1) To develop advanced skills in conducting clinical pharmacotherapy research, 2) To develop pharmacokinetic skills and to be able to apply them to bariatric surgery research, and 3) To develop advanced statistical analysis skills. To assist in the attainment of these goals, a primary mentor and three co-mentors have been selected based upon their expertise in these areas. In collaboration with these mentors, I have developed a five-year mentoring and training plan to address each goal. The career development activities and research will be carried out at the Neuropsychiatric Research Institute, Fargo, ND. This career development plan includes frequent structured meetings with each of the mentors, along with learning objectives related to each goal. The training plan also includes several proposed semester-long and short-courses, with at least one course directed toward each goal. In particular, the training plan contains a relatively high density of courses within the area of pharmacokinetics, which is necessary given the breadth of this field and my lack of research experience in this area. Several other training experiences have been included, such as multiple seminars, observations, and attendance at national conferences. Bariatric surgery procedures, in particular the Roux-en-Y Gastric Bypass (RYGBP), are widely performed and their use continues to increase. The majority of these patients take [sic] multiple medications prior to surgery and remain [sic] on some of them following surgery. Yet, the influence of RYGBP on the pharmacokinetics of the majority of medications is unknown. Changes in a medication's pharmacokinetic profile can influence the efficacy and tolerability of the medication. A large proportion of bariatric surgery candidates take an antidepressant medication preoperatively. Unlike many other classes of medications which patients often stop after surgery as comorbidities resolve, data show that the majority of patients continue to take antidepressant medication. Thus, a prospective, longitudinal trial is proposed to investigate the pharmacokinetic parameters of sertraline preoperatively and at three and 12 months following RYGBP. Through a relative bioavailability comparison of tablet and liquid sertraline preparations, and through longitudinal assessments of physiological variables of interest, this study will also provide a preliminary exploration of the potential mechanisms which produce the hypothesized pharmacokinetic changes. The experience and the data accumulated through this research, coupled with the training and mentoring provided through the career development plan, will allow me to develop an ongoing program of research in pharmacokinetics related to bariatric surgery. This will satisfy my long-term career goal of becoming an independent researcher in clinical pharmacotherapy research. Given the continual development of new medications, the evolution of bariatric surgery procedures over time, and the need to establish evidence-based medication recommendations for clinical practice, this career direction should prove fruitful on an ongoing basis.
Pharmacokinetic changes can impact the efficacy and tolerability of medications. Given the paucity of data on pharmacokinetic changes following bariatric surgery, the proposed study will provide clinically relevant information concerning this issue using the antidepressant sertraline as a test drug.
|Mitchell, James E; Roerig, James; Steffen, Kristine (2013) Biological therapies for eating disorders. Int J Eat Disord 46:470-7|
|Steffen, Kristine J; Engel, Scott G; Pollert, Garrett A et al. (2013) Blood alcohol concentrations rise rapidly and dramatically after Roux-en-Y gastric bypass. Surg Obes Relat Dis 9:470-3|
|Mitchell, James E; Crosby, Ross; de Zwaan, Martina et al. (2013) Possible risk factors for increased suicide following bariatric surgery. Obesity (Silver Spring) 21:665-72|