Our central task is to investigate the effect of genetic variants and various pathophysiological conditions on pharmacokinetics and pharmacodynamics. To this end, we conduct clinical studies on patients and healthy volunteers. Our main focus is on the drug distribution process.
To this end, we use techniques that enable direct measurement of distribution - e.g. PET or microdialysis. Our studies range from initial applications in humans to studies in a wide variety of patient populations.
Microdialysis
Microdialysis is a minimally invasive instrument for the continuous measurement of pharmacokinetics in the extracellular space of human and animal tissue. By inserting a small microdialysis catheter and taking samples for analysis, exogenous (drugs) and endogenous compounds (e.g. lactate, pyruvate, glucose, cytokines) can be determined in virtually all tissues including brain, muscle tissue, skin and fatty tissue. As a result, microdialysis has become an indispensable technique in commercial drug development and academic research.
Positron Emission Tomography (PET)
PET is a non-invasive imaging technique that can be used to track the distribution and kinetics of radioactively labelled molecules in the living organism. PET can be used to answer various questions relating to the pharmacokinetics and pharmacodynamics of drugs.
Our current research focus is the use of PET to measure the tissue distribution and pharmacokinetics of radiolabelled drugs (e.g. anti-infectives) and to investigate the functional activity of membrane transporters (ABC and SLC transporters) involved in drug transport in various organs (e.g. brain, liver, kidney, lung, eye). We work in a translational approach ranging from rodent disease models to studies in human patients (epilepsy, Alzheimer's disease). Over the last 20 years, we have brought numerous new PET tracers to first application in humans.
Clinical and preclinical PET studies are carried out in co-operation with the Department of Radiology and Nuclear Medicine, Division of Nuclear Medicine (Medical University of Vienna).
Pharmacokinetics/Pharmacodynamics (PK/PD)
In order to support clinical breakpoints and optimise therapy with a particular antimicrobial agent, the pharmacokinetic profile (which can be determined in our department by techniques such as intensive pharmacokinetic blood sampling, isolation of leukocytes, microdialysis and bronchoalveolar lavage) and its pharmacodynamic activity must be put into context. To achieve this goal, we use standard techniques such as minimum inhibitory concentration (MIC) and static time-kill curves (TKC), but also employ dynamic TKC such as hollow fibre models.
Assoc. Prof. Priv.-Doz. Dr.med.univ. Markus Zeitlinger
Head of Clinical Pharmacokinetics Working GroupHead of Department
Associate Professor
Tel.: +43 (0)1 40400-29810
E-Mail: markus.zeitlinger@meduniwien.ac.at
Researcher Profile
Selected scientifical publications
5 selected publications on pharmacokinetics and pharmacodynamics of antibiotics dated 2020 or younger:
- Matzneller P, Ngougni Pokem P, Capron A, Lackner E, Wulkersdorfer B, Nussbaumer-Pröll A, Österreicher Z, Duchek M, Van de Velde S, Wallemacq PE, Mouton JW, Van Bambeke F, Zeitlinger M. Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy volunteers after intravenous and subcutaneous administration: a randomized crossover microdialysis trial. Journal of Antimicrobial Chemotherapy. 2020 Sep 1;75(9):2650-2656. doi: 10.1093/jac/dkaa176.
- Wulkersdorfer B, Wicha SG, Kurdina E, Carrion Carrera SF, Matzneller P, Al Jalali V, Vossen MG, Riesenhuber S, Lackner E, Dorn C, Zeitlinger M. Protein binding of clindamycin in vivo by means of intravascular microdialysis in healthy volunteers. Journal of Antimicrobial Chemotherapy. 2021 Jul 15;76(8):2106-2113. doi:10.1093/jac/dkab140.
- Al Jalali V, Wölfl-Duchek M, Taubert M, Matzneller P, Lackner E, Dorn C, Kratzer A, Wulkersdorfer B, Österreicher Z, Zeitlinger M. Plasma and soft tissue pharmacokinetics of ceftolozane/tazobactam in healthy volunteers after single and multiple intravenous infusion: a microdialysis study. Journal of Antimicrobial Chemotherapy. 2021 Aug 12;76(9):2342-2351. doi: 10.1093/jac/dkab166.
- Oesterreicher Z, Eberl S, Wulkersdorfer B, Matzneller P, Eder C, van Duijn E, Vaes WHJ, Reiter B, Stimpfl T, Jäger W, Nussbaumer-Proell A, Marhofer D, Marhofer P, Langer O, Zeitlinger M. Microdosing as a Potential Tool to Enhance Clinical Development of Novel Antibiotics: A Tissue and Plasma PK Feasibility Study with Ciprofloxacin. Clin Pharmacokinet. 2022 May;61(5):697-707. doi:10.1007/s40262-021-01091-1.
- Bulman ZP, Wicha SG, Nielsen EI, Lenhard JR, Nation RL, Theuretzbacher U, Derendorf H, Tängdén T, Zeitlinger M, Landersdorfer CB, Bulitta JB, Friberg LE, Li J, Tsuji BT; International Society of Anti-Infective Pharmacology; European Society of Clinical Microbiology and Infectious Diseases Pharmacokinetics and Pharmacodynamics of Anti-Infectives Study Group; International Society of Antimicrobial Chemotherapy Anti-Infective Pharmacology Working Group. Research priorities towards precision antibiotic therapy to improve patient care. Lancet Microbe. 2022 Jun 28:S2666-5247(22)00121-5. doi: 10.1016/S2666-5247(22)00121-5.
Covid-19 associated:
- Zeitlinger M, Koch BCP, Bruggemann R, De Cock P, Felton T, Hites M, Le J, Luque S, MacGowan AP, Marriott DJE, Muller AE, Nadrah K, Paterson DL, Standing JF, Telles JP, Wölfl-Duchek M, Thy M, Roberts JA; PK/PD of Anti-Infectives Study Group (EPASG) of the European Society of Clinical Microbiology, Infectious Diseases (ESCMID). Pharmacokinetics/Pharmacodynamics of Antiviral Agents Used to Treat SARS-CoV-2 and Their Potential Interaction with Drugs and Other Supportive Measures: A Comprehensive Review by the PK/PD of Anti-Infectives Study Group of the European Society of Antimicrobial Agents. Clin Pharmacokinet. 2020 Oct;59(10):1195-1216. doi: 10.1007/s40262-020-00924-9.
- Zeitlinger M, Idzko M. Inhaled budesonide for early treatment of COVID-19. Lancet Respir Med. 2021 Jul;9(7):e59. doi: 10.1016/S2213-2600(21)00215-0.
- Wölfl-Duchek M, Bergmann F, Jorda A, Weber M, Müller M, Seitz T, Zoufaly A, Strassl R, Zeitlinger M, Herkner H, Schnidar H, Anderle K, Derhaschnig U. Sensitivity and Specificity of SARS-CoV-2 Rapid Antigen Detection Tests Using Oral, Anterior Nasal, and Nasopharyngeal Swabs: a Diagnostic Accuracy Study. Microbiol Spectr. 2022 Feb 23;10(1):e0202921. doi: 10.1128/spectrum.02029-21.
- Al Jalali V, Scherzer S, Zeitlinger M. Improved immunogenicity against SARS-CoV-2 in a solid-organ transplant recipient by switching vaccines. Clin Microbiol Infect. 2021 Oct;27(10):1529-1530. doi: 10.1016/j.cmi.2021.06.022.
- Jorda A, Zeitlinger M. Interrupting methotrexate to improve immunity after COVID-19 booster vaccination: is it really worth it? Lancet Respir Med. 2022 Sep;10(9):e80. doi: 10.1016/S2213-2600(22)00271-5.
5 selected publications on PET dated 2020 or younger:
- Viktoria Zoufal, Severin Mairinger, Mirjam Brackhan, Markus Krohn, Thomas Filip, Michael Sauberer, Johann Stanek, Thomas Wanek, Nicolas Tournier, Martin Bauer, Jens Pahnke, Oliver Langer. Imaging P-glycoprotein induction at the blood-brain barrier of a beta-amyloidosis mouse model with 11C-metoclopramide PET. J Nucl Med 61:1050-1057 (2020) DOI: 10.2967/jnumed.119.237198
- Nicolas Tournier, Sebastien Goutal, Severin Mairinger, Irene Hernández Lozano, Thomas Filip, Michael Sauberer, Fabien Caillé, Louise Breuil, Johann Stanek, Anna F. Freeman, Gaia Novarino, Charles Truillet, Thomas Wanek, Oliver Langer. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. J Cereb Blood Flow Metab 41(7):1634-1646 (2021) DOI: 10.1177/0271678X2096550
- Martin Bauer, Karsten Bamminger, Verena Pichler, Maria Weber, Simon Binder, Alexandra Maier-Salamon, Ammar Tahir, Walter Jäger, Helmuth Haslacher, Nicolas Tournier, Marcus Hacker, Markus Zeitlinger, Oliver Langer. Impaired clearance from the brain increases the brain exposure to metoclopramide in elderly subjects. Clin Pharmacol Ther 109(3):754-761 (2021) DOI: 10.1002/cpt.2052
- Severin Mairinger, Irene Hernández-Lozano, Thomas Filip, Michael Sauberer, Mathilde Löbsch, Johann Stanek, Thomas Wanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer. Impact of P-gp and BCRP on pulmonary drug disposition assessed by PET imaging in rats. J Control Release 349:109-117 (2022) DOI: 10.1016/j.jconrel.2022.06.065
- Irene Hernández-Lozano, Severin Mairinger, Thomas Filip, Mathilde Löbsch, Johann Stanek, Claudia Kuntner, Martin Bauer, Markus Zeitlinger, Marcus Hacker, Thomas H. Helbich, Thomas Wanek, Oliver Langer. Positron emission tomography-based pharmacokinetic analysis to assess renal transporter-mediated drug-drug interactions of antimicrobial drugs. Antimicrob Agents Chemother 67(3):e0149322 (2023) DOI: 10.1128/aac.01493-22
Other selected publications and reviews dated 2020 or younger:
- Jorda A, Zeitlinger M. Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antibacterial Agents: A Review. Clin Pharmacokinet. 2020 Sep;59(9):1071-1084. doi: 10.1007/s40262-020-00892-0.
- Wunderink RG, Matsunaga Y, Ariyasu M, Clevenbergh P, Echols R, Kaye KS, Kollef M, Menon A, Pogue JM, Shorr AF, Timsit JF, Zeitlinger M, Nagata TD. Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2021 Feb;21(2):213-225. doi: 10.1016/S1473-3099(20)30731-3.
- Eichler HG, Trusheim M, Schwarzer-Daum B, Larholt K, Zeitlinger M, Brunninger M, Sherman M, Strutton D, Hirsch G. Precision Reimbursement for Precision Medicine: Using Real-World Evidence to Evolve From Trial-and-Project to Track-and-Pay to Learn-and-Predict. Clin Pharmacol Ther. 2022 Jan;111(1):52-62. doi: 10.1002/cpt.2471.