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Organization / Section of Clinical Pharmacokinetics / Pharmacogenetics and Imaging
 

Clinical Pharmacokinetics /Pharmacogenetics and Imaging

Markus Zeitlinger

Markus Zeitlinger, M.D.
Associate Professor and Section Head

» Curriculum Vitae

 

 

 


Mission Statement

Our mission is to perform clinical studies in healthy volunteers and patients to elucidate the impact of genetic variants and various pathophysiological states on pharmacokinetics and pharmacodynamics.

Our main focus is the study of the drug distribution process by employing techniques to measure target site distribution directly, i.e. PET or microdialysis.

Microdialysis
Microdialysis is a minimal invasive tool for measuring pharmacokinetics continuously in the extracellular space of human and animal tissues.  By inserting a small microdialysis catheter and sampling of analyses exogenous (drugs) and endogenous compounds (e.g. lactate, pyruvate, glucose, cytokines) can be determined in virtually all tissues including brain, muscle tissue, skin and adipose tissue.  Microdialysis has thereby become an indispensable technique in commercial drug development and academic research.

In-vitro microdialysis setting to optimise experimental conditions before initiation of in-vivo pharmacokinetic studies employing microdialysis.

Positron Emission Tomography (PET)
PET is a non-invasive imaging method which allows for following the distribution and kinetics of radioactively labelled molecules in the living organism. PET can be used to answer different questions related to drug pharmacokinetics and pharmacodynamics.  Our current research focus is to use PET to study the functional activity of membrane transporters involved in drug transport (ABC and SLC transporters) in different organs (e.g. brain, liver) in a translational manner spanning all the way from rodent disease models to studies in human patients (epilepsy, Alzheimer). Clinical and preclinical PET studies are performed in cooperation with the Department of Biomedical Imaging und Image-guided Therapy, Division of Nuclear Medicine (Medical University of Vienna) and AIT Austrian Institute of Technology GmbH.

P-glycoprotein-mediated drug-drug interaction between (R)-[11C]verapamil and tariquidar at the mouse and human blood-brain barrier studied with PET (mouse PET images courtesy of AIT).

Pharmacokinetic/Pharmacodynamic (PK/PD)
In order to support clinical breakpoints and to optimize therapy with a specific antimicrobial agent the pharmacokinetic profile (which at our department can be determined by techniques like e.g. intensive pharmacokinetic blood sampling, isolation of leucocytes, microdialysis and bronchoalveolar lavage) and its pharmacodynamic activity have to be set into context. To achieve this goal we use standard techniques like the minimal inhibitory concentration (MIC) and time kill curves (TCC) but employ also dynamic TCK. A specific focus is the evaluation of the impact of protein binding on antimicrobial activity and the estimation of bacterial killing simulating physiologic conditions, e.g. by performing pharmacodynamic experiments in the presence of surfactant or at different pH values.
   

Testing of minimal inhibitory concentrations with and without addition of plasma proteins.

Pharmacogenomics
...

Detection of genes with differential response patterns during endotoxemia with different response patterns after treatment with the statin drugs

 

Key Publications

 

  1. Zeitlinger M, Schwameis R, Burian A, Burian B, Matzneller P, Müller M, Wicha WW, Strickmann DB, Prince W. Simultaneous assessment of the pharmacokinetics of a pleuromutilin, lefamulin, in plasma, soft tissues and pulmonary epithelial lining fluid. J Antimicrob Chemother. 2016 Jan 7. [Epub ahead of print] 
     
  2. Bauer M, Karch R, Zeitlinger M, Liu J, Koepp MJ, Asselin MC, Sisodiya SM, Hainfellner JA, Wadsak W, Mitterhauser M, Müller M, Pataraia E, Langer O. In vivo P-glycoprotein function before and after epilepsy surgery. Neurology. 2014 Oct 7;83(15):1326-31.</pre>
     
  3. Wressnigg N, Pöllabauer EM, Aichinger G, Portsmouth D, Löw-Baselli A, Fritsch S, Livey I, Crowe BA, Schwendinger M, Brühl P, Pilz A, Dvorak T, Singer J, Firth C, Luft B, Schmitt B, Zeitlinger M, Müller M, Kollaritsch H, Paulke-Korinek M, Esen M, Kremsner PG, Ehrlich HJ, Barrett PN. Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial. Lancet Infect Dis. 13(8):680-689 (2013)
     
  4. Bauer M, Zeitlinger M, Karch R, Matzneller P, Stanek J, Jäger W, Böhmdorfer M, Wadsak W, Mitterhauser M, Bankstahl JP, Löscher W, Koepp M, Kuntner C, Müller M, Langer O. Pgp-Mediated Interaction Between (R)-[(11)C]Verapamil and Tariquidar at the Human Blood-Brain Barrier: A Comparison With Rat Data. Clin Pharmacol Ther. Clin Pharmacol Ther. 91(2):227-233 (2012)
     
  5. Wagner CC, Simpson M, Zeitlinger M, Bauer M, Karch R, Abrahim A, Feurstein T, Schütz M, Kletter K, Müller M, Lappin G, Langer O. A Combined Accelerator Mass Spectrometry-Positron Emission Tomography Human Microdose Study with 14C- and11C-Labelled Verapamil. Clin Pharmacokinet. 50(2):111-120 (2011)  
     
  6. Ehrlich HJ, Müller M, Fritsch S, Zeitlinger M, Berezuk G, Löw-Baselli A, van der Velden MV, Pöllabauer EM, Maritsch F, Pavlova BG, Tambyah PA, Oh HM, Montomoli E, Kistner O, Noel Barrett P. A Cell Culture (Vero)-Derived H5N1 Whole-Virus Vaccine Induces Cross-Reactive Memory Responses. J Infect Dis. 200(7):1113-1118 (2009)
     
  7. Bauer M, Langer O, Dal Bianco P, Karch R, Brunner M, Abrahim A, Lanzenberger R, Hofmann A, Joukhadar C, Carminati P, Ghirardi O, Piovesan P, Forloni G, Corrado M, Lods N,  Dudczak R, Auff E, Kletter K and Müller M. A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer´s disease. Clin Pharmacol Ther 80(3):216-227 (2006)
     
  8. Zeitlinger MA, Derendorf H, Mouton JW, Cars O, Craig WA, Andes D, Theuretzbacher U. Protein binding - do we ever learn? Antimicrob Agents Chemother. 55(7):3067-3074 (2011)
     

 

For information please contact our Section Head:
Markus Zeitlinger, MD
E-Mail: markus.zeitlinger@meduniwien.ac.at

 
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