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Students

Franziska Isabelle Kluwe
Pharmacist / Freie Universität Berlin

Begin: May 2016
Supervisor: Prof. Charlotte Kloft
Co-Supervisor: Prof. Wilhelm Huisinga
Mentor: Boehringer Ingelheim

PhD Project

Optimisation of antiinfective therapies using pharmacometric models for plasma and different target-sites (working title)

Scientific interests

Despite the broad range of today’s therapeutic opportunities, the adequate treatment of infectious diseases with antiinfective drugs remains a challenging task. Although during the past decades, a number of potent new antiinfective drugs have been developed and they are frequently used, their usage still needs optimisation. For an effective and safe antiinfective therapy, the choice of the right drug against the right pathogen is only one of many contributing factors, such as the appropriate dosing regimen or individual patient characteristics. More and more, pharmacogenomic aspects, i.e. individual genetic factors such as the status of drug-metabolising enzymes and their influence on drug concentrations and responses, are also considered. In addition, effective drug concentrations at the target-site of an infection are essential, e.g. in the interstitial space fluid of a tissue, but should not exceed maximum tolerated concentrations. To determine the concentrations of a drug at the target-site, the minimally invasive technique of microdialysis is often used to continuously sample the unbound concentration of the respective drug from the interstitial space fluid.

 

The objectives of my PhD project include the analysis of data from clinical trials to develop pharmacometric models integrating samples obtained from diverse matrices, such as plasma and different target-sites. For this purpose, the nonlinear mixed-effects modelling approach is applied to describe the concentration-time profiles (pharmacokinetics) in the study population and to quantify the variability between and within the individuals (inter- and intra-individual variability).  Additionally, the identification of factors (covariates) contributing to this variability, e.g. CYP enzyme polymorphisms, shall improve our understanding of underlying mechanisms and enable more individualised therapy options. Furthermore, these population pharmacokinetic models can be linked to potential desired outcomes (pharmacodynamics), e.g. by assessing the attainment of pathogen-specific therapy targets. In a next step, simulations with the developed models shall help to evaluate the currently used dosing regimens and, if needed, develop improved dosing strategies to ultimately contribute to an optimised usage of antiinfectives.

Publications

  • Franziska Kluwe, Claudia Kirbs, Lisa Ehmann, Franziska Drescher, Peter Matzneller, Wilhelm Huisinga, Markus Zeitlinger, Charlotte Kloft.
    Population pharmacokinetics of unbound voriconazole following two different routes of administration during sequence therapy.
    26th Population Approach Group Europe Meeting (PAGE), Budapest, Hungary, 6th – 9thJune 2017. Accepted
  • Franziska Kluwe, Claudia Kirbs, Lisa Ehmann, Franziska Drescher, Johanna Weiss, Peter Matzneller, Markus Zeitlinger, Charlotte Kloft.
    Target-site pharmacokinetics of voriconazole during sequence therapy.
    27th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Vienna, Austria, 22nd – 25th April 2017.
  • Markus Oelze, Franziska I. Kluwe, Wolfgang Sippl, Andreas Hilgeroth, Robert Ramer, Burkhard Hinz, Christoph A. Ritter.
    Impact of Brk inhibition on migration and invasion of breast cancer cells.
    Annual Meeting of the Central European Society of Anticancer Drug Research (CESAR), Munich, Germany, 8th – 10th September 2016.
  • Markus Oelze, Franziska I. Kluwe, Tom Wersig, Wolfgang Sippl, Andreas Hilgeroth, Christoph A. Ritter.
    Impact of Brk-inhibitors on nondirectional and directed migration of breast cancer cells.
    107th Annual Meeting of the American Association for Cancer Research, New Orleans, USA, 16th – 20th April 2016.
  • Franziska I. Kluwe.
    Optimierung von In-vitro-Testsystemen der Zellmigration und Untersuchung des Einflusses von PTK6-/Brk-Hemmstoffen auf das Migrationsverhalten von Brustkrebszelllinien.
    Ernst-Moritz-Arndt-Universität Greifswald (2016).

Education

  • Since 06/2016: PhD student at the Graduate Research Training Program “PharMetrX: Pharmacometrics & Computational Disease Modelling“ at the Dept. of Clinical Pharmacy & Biochemistry supervised by Prof. Dr. Charlotte Kloft at the Freie Universitaet Berlin
  • 06/2016: Degree as Diploma-Pharmacist at Ernst-Moritz-Arndt-Universitaet Greifswald, Germany
  • 05/2016: Registration as Pharmacist
  • 11/2015 – 04/2016: Pre-registration internship at BerlinApotheke am Garbátyplatz in Berlin
  • 05/2015 – 10/2015: Diploma thesis at the Dept. of Clinical Pharmacy supervised by Prof. Dr. Christoph A. Ritter at the Ernst-Moritz-Arndt-Universitaet Greifswald, Germany
    Topic: “Optimisation of in vitro test systems of cell migration and impact of novel PTK6-/Brk-inhibitors on cell migration of breast cancer cell lines”
  • 10/2010 – 04/2015: Degree in Pharmacy at Ernst-Moritz-Arndt-Universitaet Greifswald, Germany
  • 06/2010: A-Level (Abitur) at  Rosa-Luxemburg-Oberschule (Gymnasium) in Berlin, Germany