Translational PKPD
Health and diseases
Translational PKPD
Our research focuses on understanding the fundamental and functional aspects of pharmacokinetics-pharmacodynamics (PKPD) in health and disease.
Within the area of translational PKPD we address conversion of pharmacokinetic data from the preclinical to the clinical setting. This is strongly needed for optimizing drug discovery processes and promoting efficient treatment of CNS diseases.
We are interested in brain drug delivery in relation to transport processes of both small and large molecules across the blood-brain barrier (BBB). Using the concepts and methodologies developed in the group, we are exploring brain regional drug disposition, including the influence of diseases, with focus on the pharmacologically relevant unbound concentrations. We are also studying the quantitative role of nanocarriers for improved uptake into the brain.
Our work also emphasizes the importance of bridging the expertise within academia and pharmaceutical industry in order to seek excellence in method development for better therapeutics treating CNS disorders.
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Publications
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Holder, Brianna M.; Tolan, Shaina E.; Heinrich, Kaleb K.; Miller, Kaitlin C.; Hudson, Natalie; Nehra, Geetika; Pizzo, Michelle E.; Storck, Steffen E.; Elmquist, William F.; Engelhardt, Britta; Loryan, Irena; Toborek, Michal; Bauer, Bjoern; Hartz, Anika M. S.; Kim, Brandon J.
Brain barriers virtual: an interim solution or future opportunity?
2022
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Backstrom, E.; Erngren, T.; Fihn, B-M; Sadiq, M. W.; Lindberg, W.; Fridén, Markus; Grime, K.
Possible Extraction of Drugs from Lung Tissue During Broncho-alveolar Lavage Suggest Uncertainty in the Procedure's Utility for Quantitative Assessment of Airway Drug Exposure
2022
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Loryan, Irena; Smith, David E.; Artursson, Per; Breimer, Douwe; Deguchi, Yoshiharu; Paalzow, Lennart; Sugiyama, Yuichi; Terasaki, Tetsuya; de Lange, Elizabeth C. M.
Professor Margareta Hammarlund-Udenaes - Humbled Scientist Shaping Modern Neuropharmacokinetics
2022
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Syvänen, Stina; Fridén, Markus
Professor Margareta Hammarlund-Udenaes: a Modern and Visionary Mentor
2022
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Loryan, Irena; Reichel, Andreas; Feng, Bo; Bundgaard, Christoffer; Shaffer, Christopher; Kalvass, Cory; Bednarczyk, Dallas; Morrison, Denise; Lesuisse, Dominique; Hoppe, Edmund; Terstappen, Georg C.; Fischer, Holger; Di, Li; Colclough, Nicola; Summerfield, Scott; Buckley, Stephen T.; Maurer, Tristan S.; Fridén, Markus
Unbound Brain-to-Plasma Partition Coefficient, K-p,K-uu,K-brain-a Game Changing Parameter for CNS Drug Discovery and Development
2022
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de Lange, Elizabeth C. M.; Hammarlund-Udenaes, Margareta
Understanding the Blood-Brain Barrier and Beyond: Challenges and Opportunities for Novel CNS Therapeutics
2022
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Wieslander, Håkan; Harrison, Philip J.; Skogberg, Gabriel; Jackson, Sonya; Fridén, Markus; Karlsson, Johan; Spjuth, Ola; Wählby, Carolina
Deep learning and conformal prediction for hierarchical analysis of large-scale whole-slide tissue images
2021
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Sadiq, Muhammad Waqas; Holz, Olaf; Ellinghusen, Birthe D.; Faulenbach, Cornelia; Mueller, Meike; Badorrek, Philipp; Eriksson, Ulf G.; Fridén, Markus; Stomilovic, Stina; Lundqvist, Anders J.; Hohlfeld, Jens M.
Lung pharmacokinetics of inhaled and systemic drugs: A clinical evaluation
2021
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Luptáková, Dominika; Vallianatou, Theodosia; Nilsson, Anna; Shariatgorji, Reza; Hammarlund-Udenaes, Margareta; Loryan, Irena; Andrén, Per E.
Neuropharmacokinetic visualization of regional and subregional unbound antipsychotic drug transport across the blood-brain barrier.
2021
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Loryan, Irena; Hammarlund-Udenaes, Margareta; Syvänen, Stina
Brain Distribution of Drugs:: Pharmacokinetic Considerations
2020
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Syvänen, Stina; Hammarlund-Udenaes, Margareta; Loryan, Irena
In Vivo Studies of Drug BBB Transport:: Translational Challenges and the Role of Brain Imaging
2020
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Nyman, Elin; Lindh, Maria; Lövfors, William; Simonsson, Christian; Persson, Alexander; Eklund, Daniel; Bäckström, Erica; Fridén, Markus; Cedersund, Gunnar
Mechanisms of a sustained anti-inflammatory drug response in alveolar macrophages unraveled with mathematical modeling
2020
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Andronis, Christos; Silva, João Pedro; Lekka, Eftychia; Virvilis, Vassilis; Carmo, Helena; Bampali, Konstantina; Ernst, Margot; Hu, Yang; Loryan, Irena; Richard, Jacques; Carvalho, Félix; Savić, Miroslav M
Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis
2020
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Hu, Yang; Hammarlund-Udenaes, Margareta
Perspectives on Nanodelivery to the Brain: Prerequisites for Successful Brain Treatment
2020
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Hamm, Gregory R.; Bäckström, Erica; Brülls, Mikael; Nilsson, Anna; Strittmatter, Nicole; Andrén, Per E.; Grime, Ken; Fridén, Markus; Goodwin, Richard J. A.
Revealing the Regional Localization and Differential Lung Retention of Inhaled Compounds by Mass Spectrometry Imaging
2020
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Sulku, Johanna; Jansson, Christer; Melhus, Håkan; Malinovschi, Andrei; Ställberg, Björn; Bröms, Kristina; Högman, Marieann; Lisspers, Karin; Hammarlund-Udenaes, Margareta; Nielsen, Elisabet I.
A Cross-Sectional Study Assessing Appropriateness Of Inhaled Corticosteroid Treatment In Primary And Secondary Care Patients With COPD In Sweden
2019
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Mantas, Athanasios; Labbe, Valentine; Loryan, Irena; Mihranyan, Albert
Amorphisation of Free Acid Ibuprofen and Other Profens in Mixtures with Nanocellulose: Dry Powder Formulation Strategy for Enhanced Solubility
2019
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Colcloughl, Nicola; Chen, Kan; Johnstrom, Peter; Fridén, Markus; McGinnity, Dermot F.
Building on the success of osimertinib: achieving CNS exposure in oncology drug discovery
2019
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Ganguly, Koustav; Carlander, Ulrika; Garessus, Estella D. G.; Fridén, Markus; Eriksson, Ulf G.; Tehler, Ulrika; Johanson, Gunnar
Computational modeling of lung deposition of inhaled particles in chronic obstructive pulmonary disease (COPD) patients: identification of gaps in knowledge and data
2019
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Gustafsson, Sofia; Sehlin, Dag; Lampa, Erik; Hammarlund-Udenaes, Margareta; Loryan, Irena
Heterogeneous drug tissue binding in brain regions of rats, Alzheimer’s patients and controls: impact on translational drug development
2019
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Puris, Elena; Gynther, Mikko; de Lange, Elizabeth C. M.; Auriola, Seppo; Hammarlund-Udenaes, Margareta; Huttunen, Kristiina M.; Loryan, Irena
Mechanistic Study on the Use of the L-Type Amino Acid Transporter 1 for Brain Intracellular Delivery of Ketoprofen via Prodrug: A Novel Approach Supporting the Development of Prodrugs for Intracellular Targets
2019
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Schou, Magnus; Ewing, Par; Cselenyi, Zsolt; Fridén, Markus; Takano, Akihiro; Halldin, Christer; Farde, Lars
Pulmonary PET imaging confirms preferential lung target occupancy of an inhaled bronchodilator
2019
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Yusof, Siti R; Mohd Uzid, Mahathir; Teh, Eng-Huat; Hanapi, Nur Aziah; Mohideen, Mazlin; Mohamad Arshad, Ahmad Saifuddin; Mordi, Mohd Nizam; Loryan, Irena; Hammarlund-Udenaes, Margareta
Rate and extent of mitragynine and 7-hydroxymitragynine blood-brain barrier transport and their intra-brain distribution: the missing link in pharmacodynamic studies
2019
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Hu, Yang; Gaillard, Pieter J.; De lange, Elizabeth C.M.; Hammarlund-Udenaes, Margareta
Targeted Brain Delivery of Methotrexate by Glutathione PEGylated Liposomes: How can the Formulation Make a Difference?
2019
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Hu, Yang; Hammarlund-Udenaes, Margareta; Fridén, Markus
Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling.
2019
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Gustafsson, Sofia; Gustavsson, Tobias; Roshanbin, Sahar; Hultqvist, Greta; Hammarlund-Udenaes, Margareta; Sehlin, Dag; Syvänen, Stina
Blood-Brain Barrier Integrity in a Mouse Model of Alzheimer’s Disease With or Without Acute 3D6 Immunotherapy
2018
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Hu, Yang; Gaillard, Pieter J.; Rip, Jaap; De lange, Elizabeth C.M.; Hammarlund-Udenaes, Margareta
In Vivo Quantitative Understanding of PEGylated Liposome’s Influence on Brain Delivery of Diphenhydramine
2018
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Gustafsson, Sofia; Lindström, Veronica; Ingelsson, Martin; Hammarlund-Udenaes, Margareta; Syvänen, Stina
Intact blood-brain barrier transport of small molecular drugs in animal models of amyloid beta and alpha-synuclein pathology
2018
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Mihajlica, Nebojsa; Betsholtz, Christer; Hammarlund-Udenaes, Margareta
Pharmacokinetics of Pericyte Involvement in Small-Molecular Drug Transport Across the Blood-Brain Barrier
2018
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Boger, Elin; Fridén, Markus
Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Accurately Predicts the Better Bronchodilatory Effect of Inhaled Versus Oral Salbutamol Dosage Forms
2018
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Mihajlica, Nebojsa; Betsholtz, Christer; Hammarlund-Udenaes, Margareta
Rate of Small-Molecular Drug Transport Across the Blood-Brain Barrier in a Pericyte-Deficient State
2018
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Bäckström, Erica; Hamm, Gregory; Nilsson, Anna; Fihn, Britt-Marie; Strittmatter, Nicole; Andrén, Per; Goodwin, Richard J. A.; Fridén, Markus
Uncovering the regional localization of inhaled salmeterol retention in the lung
2018
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Ericsson, Therese; Fridén, Markus; Kärrman-Mårdh, Carina; Dainty, Ian; Grime, Ken
Benchmarking of Human Dose Prediction for Inhaled Medicines from Preclinical In Vivo Data
2017
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Gustafsson, Sofia; Eriksson, Jonas; Syvänen, Stina; Eriksson, Olof; Hammarlund-Udenaes, Margareta; Antoni, Gunnar
Combined PET and microdialysis for in vivo estimation of drug blood-brain barrier transport and brain unbound concentrations
2017
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Ehrhardt, Carsten; Backman, Per; Couet, William; Edwards, Chris; Forbes, Ben; Fridén, Markus; Gumbleton, Mark; Hosoya, Ken-Ichi; Kato, Yukio; Nakanishi, Takeo; Takano, Mikihisa; Terasaki, Tetsuya; Yumoto, Ryoko
Current Progress Toward a Better Understanding of Drug Disposition Within the Lungs: Summary Proceedings of the First Workshop on Drug Transporters in the Lungs
2017
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Greenwood, John; Hammarlund-Udenaes, Margareta; Jones, Hazel C.; Stitt, Alan W.; Vandenbrouke, Roosmarijn E.; Romero, Ignacio A.; Campbell, Matthew; Fricker, Gert; Brodin, Birger; Manninga, Heiko; Gaillard, Pieter J.; Schwaninger, Markus; Webster, Carl; Wicher, Krzysztof B.; Khrestchatisky, Michel
Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017
2017
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Chen, Xiaomei; Keep, Richard F.; Liang, Yan; Zhu, Hao-Jie; Hammarlund-Udenaes, Margareta; Hu, Yongjun; Smith, David E.
Influence of peptide transporter 2 (PEPT2) on the distribution of cefadroxil in mouse brain: A microdialysis study
2017
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Hammarlund-Udenaes, Margareta
Microdialysis as an Important Technique in Systems Pharmacology: a Historical and Methodological Review
2017
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Kusuhara, Hiroyuki; Obach, R. Scott; Rostami-Hodjegan, Amin; Pang, K. Sandy; Hammarlund-Udenaes, Margareta; Derendorf, Hartmut; Artursson, Per; Huang, Shiew-Mei; Suzuki, Hiroshi; Terasaki, Tetsuya
Professor Yuichi Sugiyama: A Brilliant, Creative, Amicable, Charming, and Humorous Pharmaceutical Scientist
2017
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Loryan, Irena; Hoppe, Edmund; Hansen, Klaus; Held, Felix; Kless, Achim; Linz, Klaus; Marossek, Virginia; Nolte, Bert; Ratcliffe, Paul; Saunders, Derek; Terlinden, Rolf; Wegert, Anita; Welbers, André; Will, Olaf; Hammarlund-Udenaes, Margareta
Quantitative Assessment of Drug Delivery to Tissues and Association with Phospholipidosis: A Case Study with Two Structurally Related Diamines in Development
2017
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Agrawal, Mukta; Ajazuddin, A; Tripathi, Dulal K.; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G.; Mourtas, Spyridon; Hammarlund-Udenaes, Margareta; Alexander, Amit
Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease
2017
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Chen, Xiaomei; Slättengren, Tim; de Lange, Elizabeth C. M.; Smith, David E.; Hammarlund-Udenaes, Margareta
Revisiting atenolol as a low passive permeability marker
2017
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Hu, Yang; Rip, Jaap; Gaillard, Pieter J.; de lange, Elizabeth C. M.; Hammarlund-Udenaes, Margareta
The Impact of Liposomal Formulations on the Release and Brain Delivery of Methotrexate: An In Vivo Microdialysis Study
2017
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Bäckström, Erica; Lundqvist, Anders; Boger, Elin; Svanberg, Petter; Ewing, Pär; Hammarlund-Udenaes, Margareta; Fridén, Markus
Development of a Novel Lung Slice Methodology for Profiling of Inhaled Compounds
2016
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Lindqvist, Annika; Jönsson, Siv; Hammarlund-Udenaes, Margareta
Exploring Factors Causing Low Brain penetration of the Opioid Peptide DAMGO through Experimental Methods and Modeling
2016
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Melander, Erik; Eriksson, Camilla; Jansson, Britt; Göransson, Ulf; Hammarlund-Udenaes, Margareta
Improved method for quantitative analysis of the cyclotide kalata B1 in plasma and brain homogenate
2016
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Lindqvist, Annika; Rip, Jaap; van Kregten, Joan; Gaillard, Pieter J; Hammarlund-Udenaes, Margareta
In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes
2016
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Loryan, Irena; Melander, Erik; Svensson, M.; Payan, M.; König, F.; Jansson, Britt; Hammarlund-Udenaes, Margareta
In-depth neuropharmacokinetic analysis of antipsychotics based on a novel approach to estimate unbound target-site concentration in CNS regions: link to spatial receptor occupancy
2016
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Bäckström, Erica; Boger, Elin; Lundqvist, Anders; Hammarlund-Udenaes, Margareta; Fridén, Markus
Lung Retention by Lysosomal Trapping of Inhaled Drugs Can Be Predicted In Vitro With Lung Slices
2016
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Lindqvist, Annika; Fridén, Markus; Hammarlund-Udenaes, Margareta
Pharmacokinetic Considerations of Nanodelivery to the Brain: Using Modeling and Simulations to Predict Outcome of Liposomal Formulations
2016