A Pharmacokinetic Comparison of Sertraline Before and After Bariatric Surgery

舍曲林减肥手术前后的药代动力学比较

• 批准号: 8235052
• 负责人: KRISTINE Jayne STEFFEN
• 金额: $ 13.49万
• 依托单位: SANFORD RESEARCH NORTH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8235052
• 关键词: Address; Adult; Algorithms; Antidepressive Agents; Area; Biological Availability; Body Composition; Body Weight; Body Weight decreased; Clinical; Collaborations; Collection; Comorbidity; Complex; Coupled; Data; Development; Development Plans; Dose; Drug Kinetics; Evolution; FarGo; Fatty acid glycerol esters; Fostering; Gastric Bypass; Goals; Guidelines; Health; Hepatic; Hour; Individual; Learning; Liquid substance; Managed Care; Measures; Medication Management; Mentors; Obesity; Operative Surgical Procedures; Parents; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Plasma; Plasma Proteins; Preparation; Procedures; Recommendation; Regimen; Relative (related person); Repeat Surgery; Research; Research Activity; Research Institute; Research Personnel; Research Training; Resolution; Sampling; Sertraline; Solutions; Structure; Tablets; Therapeutic; Time; Training; bariatric surgery; base; career; career development; clinical practice; clinically relevant; density; design; dosage; drug testing; evidence base; evidence based guidelines; experience; follow-up; improved; interest; meetings; neuropsychiatry; programs; prospective; skills; suicidal risk; symposium; tablet formulation

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.

描述（由申请人提供）： 该建议旨在提供一项全面的培训和研究计划，这将促进我在临床药物治疗研究领域成为独立研究者的长期职业目标。为了实现这一目标，已经制定了三个短期目标：1）开发进行临床药物治疗研究的先进技能，2）发展药代动力学技能并能够将其应用于减肥手术研究，以及3）开发先进的统计分析技能。为了协助实现这些目标，根据他们在这些领域的专业知识，选择了一位主要导师和三名副主管。与这些导师合作，我制定了一个为期五年的指导和培训计划来解决每个目标。职业发展活动和研究将在ND Fargo的Neuropsychiatric Research Institute进行。该职业发展计划包括与每个导师的频繁结构会议，以及与每个目标相关的学习目标。培训计划还包括几个拟议的学期和短赛季，至少有一门课程针对每个目标。特别是，培训计划在药代动力学领域内包含相对较高的课程密度，鉴于该领域的广度以及我在该领域缺乏研究经验，这是必要的。还包括其他几项培训经验，例如多个研讨会，观察和参加全国会议。减肥手术程序，尤其是Roux-en-Y胃旁路（RYGBP），已广泛执行，其使用持续增加。这些患者中的大多数在手术前服用了多种药物，并在手术后的一些药物上保留。然而，RYGBP对大多数药物药代动力学的影响尚不清楚。药物的药代动力学特征的变化会影响药物的功效和耐受性。大部分的减肥手术候选者术前服用抗抑郁药。与许多其他类型的药物不同，患者经常在手术后随着合并症的解决，数据表明，大多数患者继续服用抗抑郁药。因此，提出了一项前瞻性的纵向试验，以研究术前舍法林的药代动力学参数，在RYGBP后三个月和12个月中。通过对片剂和液体舍曲林制剂的相对生物利用度比较，以及通过对感兴趣的生理变量的纵向评估，本研究还将对产生假设的药物动力学变化的潜在机制进行初步探索。通过这项研究积累的经验和数据，再加上通过职业发展计划提供的培训和指导，将使我能够制定一项与减肥手术有关的药代动力学研究计划。这将满足我成为临床药物治疗研究独立研究人员的长期职业目标。鉴于新药物的持续开发，减肥手术程序的演变随着时间的流逝，以及为临床实践建立基于证据的药物建议的需求，这种职业方向应持续证明富有成效。 公共卫生相关性： 药代动力学的变化会影响药物的功效和耐受性。鉴于减肥手术后有关药代动力学变化的数据很少，拟议的研究将提供有关使用抗抑郁药舍曲林作为测试药物的临床相关信息。