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Students

Ana-Marija Grišić
Pharmacist / Freie Universität Berlin

Begin: March 2016
Supervisor: Prof. Charlotte Kloft
Co-Supervisor: Prof. Wilhelm Huisinga
Mentor: Merck

PhD Project

Pharmacokinetic and pharmacodynamic modelling of monoclonal antibodies (working title)

Scientific interests

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that affects the gastrointestinal tract. There are two main forms of the disease, Crohn’s disease and Ulcerative colitis, which differ in symptoms and location of the inflammation. In the gastrointestinal tract of the patients with IBD increased cytokine expression (e.g., tumor necrosis factor alpha, TNF) and elevated number of immune cells are present. The symptoms that patients most often experience include diarrhea, abdominal pain, malnutrition and fatigue.

Immunosuppressive and anti-inflammatory agents are used as standard treatment for IBD. However, in many patients the response to this treatment is absent or fades over time. As substitute for the standard therapy, certain monoclonal antibodies (mAbs) are employed. These antibodies are therapeutic proteins that bind with high specificity to their targets. Together with long half-lives, this characteristic makes them promising pharmaceuticals. One such mAb is infliximab, an IgG1 mAb against TNFα.

Due to lack of information necessary for successful treatment of IBD with mAbs, further studies are needed in order to complete the knowledge and develop an optimal dosing strategy. Immunogenicity and generation of anti-drug antibodies (ADAs) as well as their effect on pharmacokinetics and pharmacodynamics of mAbs are among the questions that require further investigation.

Mixed-effect modelling is a powerful approach for analysis of clinical data that are sparse, which is usually the case with mAbs related data. Moreover, this method enables evaluation of the influence of patient specific characteristics (covariates) on the pharmacokinetics, pharmacodynamics and disease progression.

The focus of my PhD will be on the evaluation of population pharmacokinetic covariates and assessment of the effect of ADAs on the pharmacokinetics of mAbs. The results should provide us with guidance on how to use infliximab more efficiently as well as to broaden our knowledge about pharmacokinetics of infliximab.

Presentations

Education

  • Since 03/2016: PhD Student (Graduate Research Training Program “PharMetrX: Pharmacometrics & Computational Disease Modeling”) at the Freie Universitaet Berlin, Dept. of Clinical Pharmacy and Biochemistry supervised by Prof. Dr. Charlotte Kloft
  • 11/2014-02/2015: German language certificate (CEFR B2), Ludwig-Maximilians Universitaet Muenchen, Germany
  • 08/2013-09/2013: Internship at the Institute of Pharmacy, Biopharmacy group, supervised by Prof. Dr. rer. nat. habil. Dr. h. c. R. Neubert, Martin-Luther-Universitaet Halle-Wittenberg, Germany
  • 10/2009-07/2014: Master of Pharmacy, Univerzitet u Novom Sadu (University of Novi Sad), Serbia
  • 02/2009: Certificate in Advanced English (CEFR C1), University of Cambridge ESOL Examinations