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Students

David Busse
MSc Pharmaceutical Science / Freie Universität Berlin

PharMetrX Research+ Student
PhD student year: 2018

Home University: Freie Universität Berlin
Supervisor: Prof. Charlotte Kloft
Co-Supervisor: Prof. Wilhelm Huisinga
Mentoring I-Partner: Boehringer Ingelheim

PhD Project

Optimisation of therapy for selected antibiotics in special patient populations using nonlinear mixed-effects modelling (working title)

Scientific interests

Morbidly obese patients represent a growing but understudied patient population with sparse and oftentimes contradicting information in the field of antiinfective therapy. To guarantee effective and safe treatment of bacterial infections targeted patient and pathogen specific antibiotic therapy is crucial.

For a pathogen specific therapy not only the antimicrobial spectrum of the drug but also adequacy of the dosing regimen and the resulting effective drug concentration-time profile at the target site are important. To measure effective drug concentration at target site, in case of antiinfectives mostly the extracellular interstitial fluid in the tissue, the minimally invasive method microdialysis is selected.

Regarding patient specific antibiotic therapy the oftentimes significant variability of the drug concentration-time profile is of interest. Employing standard dosing regimens bears the risk of subtherapeutic or toxic concentration-time profiles which might lead to therapy failure, increased occurrence of adverse events and development of bacterial resistance.

My dissertation project includes the pharmacometric analysis of frequently employed antibiotics after standard dosing regimens in morbidly obese patients. Based on clinical data on plasma and target site drug concentrations using microdialysis nonlinear mixed effects models will be developed. In a first step the pharmacokinetics of the antibiotics will be characterised, i.e. the population specific concentration-time profile and the different levels of variability between and within patients. In a second step patient specific covariates (e.g. markers of organ function or disease status) will be identified, which explain inter- and intraindividual variability and their impact on model parameters will be quantified.

Simulations based on the developed model can be utilised to evaluate dosing regimens regarding achieving effective pathogen specific drug concentration-time profiles (pharmacodynamics/pharmacokinetic targets) in morbidly obese patients. If need be alternative adequate dosing regimen with reduced adverse events can be suggested. In such an integrative manor knowledge spanning different classes of antibiotics shall be generated. Additionally the aim is to guarantee antiinfective therapy success in this patient population and to reduce the development of further antibiotic resistance.

Publications

Please see the list of all publications and PhD theses.

Education

  • Since 07/2018: PhD student of the Graduate Research Training Program “PharMetrX: Pharmacometrics & Computational Disease Modelling“ supervised by Prof. Dr. Charlotte Kloft at the Dept. of Clinical Pharmacy & Biochemistry, Freie Universitaet Berlin
  • 09/2016-06/2018: Innovative Medicines Graduate trainee at AstraZeneca AB, Sweden
  • 03/2016-08/2016: Master Thesis at AstraZeneca AB, Sweden
  • 10/2014-08/2016: Master of Pharmaceutical Sciences, Westfälische Wilhelms-Universität Münster
  • 02/2014-09/2014: Exchange semester at the University of Gothenburg
  • 10/2011-09/2014: Bachelor of Applied Science in Molecular Biology, Georg-August-Universität Göttingen