Keywords

ATP-Binding Cassette Transporters; Biological Psychiatry; Blood-Brain Barrier; Blood-Retinal Barrier; Clinical Trial, Phase I; Clinical Trial, Phase II; Drug Interactions; Drug Resistance; Epilepsy, Temporal Lobe; Ethics; Ethics Committees; Genetics; Liver; Microdialysis; Organic Anion Transporters; P-Glycoprotein; Pharmacogenetics; Pharmacokinetics; Positron-Emission Tomography; Schizophrenia and Disorders with Psychotic Features

Research group(s)

• Section of Clinical Pharmacokinetics / Pharmacogenetics and Imaging
  Head: Markus Zeitlinger
  Research Area: 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.
  Members:
  Alina Nussbaumer-Pröll
  Irene Hernandez-Lozano
  Martin Bauer
  Severin Mairinger
  Valentin al Jalali
  Oliver Langer

Research interests

A critical piece in drug discovery and development is conducting pharmacokinetics and drug metabolism studies. Studies with focus on ADME (Absorption, Distribution, Metabolism, Elimination) help to determine blood and target site distribution of a drug candidate in adition to the safety and tollerability profile in humans. 
Imaging of transporters influencing the target tissue pharmacokinetics of ABC and OATP substrates is another core expertise of our research group. Functional alteration of transporter processes such as up- or down regulation are often observed in healthy aging, various pathophysiological states and may contribute to pharmacoresistancy, drug-drug interactions or vulnerability towards diseases or drug side effects. Thus, the characterization of transporter function and modulation of transporter activity are another focus of our work.
By way of cooperation with the Department of Psychiatry and Psychotherapy we offer pharmacogenetic and therapeutic drug monitoring guided treatment optimisation for patients at the "Pharmacogenetic Outpatients Clinic". 

Techniques, methods & infrastructure

Positron-emission tomography (PET) and magnete resonance iamging (MRI) are valuable tools to investigate such processes involved in the absorption, distribution, metabolism, and excretion of a pharmaceutical compound within the human organism. Based on the microdosing concept only sub pharmacological doses of a radiolabelled compound are used to investigate drug distribution and pharmacokinetics in healthy vlunteers and patients. This study setup eases first in human trials and first application of a novel radiotracer for clinical PET imaging.

Drug levels in plasma, other body fluids or microdialysis samples are analyzed with LC-MS/MS or LC-MS/AMS (for ¹⁴C-labelled substances only).

Selected publications

1. Bauer, M. et al., 2021. Impaired Clearance From the Brain Increases the Brain Exposure to Metoclopramide in Elderly Subjects. Clinical Pharmacology & Therapeutics, 109(3), pp.754–761. Available at: http://dx.doi.org/10.1002/cpt.2052.
2. Bauer, M., Tournier, N. & Langer, O., 2019. Imaging P‐Glycoprotein Function at the Blood–Brain Barrier as a Determinant of the Variability in Response to Central Nervous System Drugs. Clinical Pharmacology & Therapeutics. Available at: http://dx.doi.org/10.1002/cpt.1402.
3. Bauer, M. et al., 2014. In vivo P-glycoprotein function before and after epilepsy surgery. Neurology, 83(15), pp.1326-1331. Available at: http://dx.doi.org/10.1212/WNL.0000000000000858.
4. Bauer, M. et al., 2018. A Proof-of-Concept Study to Inhibit ABCG2- and ABCB1-Mediated Efflux Transport at the Human Blood-Brain Barrier. Journal of Nuclear Medicine, p.jnumed.118.216432. Available at: http://dx.doi.org/10.2967/jnumed.118.216432.
5. Bauer, M. et al., 2018. Effect of Rifampicin on the Distribution of [11C]Erlotinib to the Liver, a Translational PET Study in Humans and in Mice. Molecular Pharmaceutics, 15(10), pp.4589–4598. Available at: http://dx.doi.org/10.1021/acs.molpharmaceut.8b00588.