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; Organic Anion Transporters; P-Glycoprotein; 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:
  Martin Bauer
  Oliver Langer

Research interests

Imaging of transporters influencing the target tissue pharmacokinetics of ABC and OATP substrates is our core expertise. Functional alteration of transporter processes such as up- or down regulation are often observed in 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.

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.

Selected publications

1. Bauer, M. et al., 2020. 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.