Daniel Röshammar

Drug Safety Assessment Based on Target Affinity, Drug Exposure and Plasma Protein Binding: Drug-Induced Cardiotoxicity from a Translational Pharmacology Perspective

Simona Catozzi, Fianne Sips, Niccolò Totis, Marc-Antonio Bisotti et autres

Cardiac safety assessment is an integral part of drug discovery and development. Drug candidates that adversely affect cardiac or hemodynamic function should be discontinued early unless a favorable benefit-risk ratio for patients can be justified. In this hypothesis-generating work, we aimed to …

it, nl, us (code pays fourni par la source)

NX210c Demonstrates Therapeutic Potential to Restore Blood–Brain Barrier in a QSP Model of Relapsing–Remitting Multiple Sclerosis

Giulia Russo, Fianne L. P. Sips, Simona Catozzi, Pauline Bambury et autres

Blood-brain barrier (BBB) breakdown is a hallmark of several neurological disorders, including multiple sclerosis (MS). NX210c, a novel therapeutic peptide, has shown promise in restoring BBB integrity, in both preclinical and clinical settings, offering potential for use in MS populations and across …

it, nl, fr (code pays fourni par la source)

A Case Study Showcasing the Impact of the InSilicoTrials Platform on Obesity Clinical Trials

Jane Knöchel, Pauline Bambury, Maud Bénéton, Paolo Messina et autres

Objectives: Interactive applications using Shiny in R transform pharmacometric model simulations by enabling dynamic user interfaces that update simulations in real-time. Despite advancements in R packages like mrgsolve and rxode2, challenges persist, particularly for mechanistic and AI/ML models. The InSilicoTrials (IST) platform …

it (code pays fourni par la source)

Transforming Pediatric Rare Disease Drug Development: Enhancing Clinical Trials and Regulatory Evidence With Virtual Patients

Fianne L. P. Sips, Marco Virgolin, Giuseppe Pasculli, Federico Reali et autres

Drug development in pediatric rare diseases is complicated by practical and ethical constraints on clinical trial design, stemming from small, highly heterogeneous, and vulnerable patient populations. Virtual patients (VPs) created with machine-learning (ML), mechanistically driven computational approaches, or hybrids thereof, have the …

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Optimized infusion rates for N,N‐dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and simulation framework

Emma Eckernäs, Jeroen V. Koomen, Christopher Timmermann, Robin Carhart‐Harris et autres

N,N-dimethyltryptamine (DMT) is a psychedelic compound that is being studied as a therapeutic option in various psychiatric disorders. Due to its short half-life, continuous infusion of DMT has been proposed to extend the psychedelic experience and potential therapeutic effects. The primary aim …

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N,N‐dimethyltryptamine affects electroencephalography response in a concentration‐dependent manner—A pharmacokinetic/pharmacodynamic analysis

Emma Eckernäs, Christopher Timmermann, Robin Carhart‐Harris, Daniel Röshammar et autres

Abstract N,N‐dimethyltryptamine (DMT) is a psychedelic substance and is being used as a research tool in investigations of the neurobiology behind the human consciousness using different brain imaging techniques. The effects of psychedelics have commonly been studied using electroencephalography (EEG) and have …

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Population pharmacokinetic/pharmacodynamic modeling of the psychedelic experience induced by N,N‐dimethyltryptamine – Implications for dose considerations

Emma Eckernäs, Christopher Timmermann, Robin Carhart‐Harris, Daniel Röshammar et autres

Abstract N,N‐dimethyltryptamine (DMT) is a psychedelic compound that is believed to have potential as a therapeutic option in several psychiatric disorders. The number of clinical investigations with DMT is increasing. However, very little is known about the pharmacokinetic properties of DMT as …

se, gb, us (code pays fourni par la source)

Anticoagulant Effects of Dabigatran on Coagulation Laboratory Parameters in Pediatric Patients: Combined Data from Five Pediatric Clinical Trials

Lesley Mitchell, Daniel Röshammar, Fenglei Huang, Manuela Albisetti et autres

BACKGROUND: Dabigatran etexilate, a direct oral thrombin inhibitor, is approved to treat venous thromboembolism (VTE) in both adults and children. OBJECTIVES: This population analysis characterized relationships between dabigatran total plasma concentrations and coagulation laboratory parameters (activated partial thromboplastin time [aPTT]; diluted thrombin …

ca, us, ch, gb, it, de (code pays fourni par la source)

Pharmacokinetic modeling and simulation support for age‐ and weight‐adjusted dosing of dabigatran etexilate in children with venous thromboembolism

Daniel Röshammar, Fenglei Huang, Manuela Albisetti, Lisa Bomgaars et autres

BACKGROUND: Dabigatran etexilate (DE), a direct oral thrombin inhibitor, has been evaluated in children with venous thromboembolism (VTE) using oral solution, pellets, or capsules. OBJECTIVES: This study evaluated DE pharmacokinetics (PK) in children with VTE and the appropriateness of a DE pediatric …

us, ch, gb, it, ca, Égypte, de (code pays fourni par la source)

Pharmacokinetic Modelling and Simulation Support the Age and Body-Weight-Adjusted Dosing of Dabigatran Etexilate in Pediatric Patients with Venous Thromboembolism

Daniel Röshammar

Pharmacokinetic–pharmacodynamic modelling of platelet response to ticagrelor in stable coronary artery disease and prior myocardial infarction patients

Magnus Åstrand, Carl Amilon, Daniel Röshammar, Anders Himmelmänn et autres

AIMS: To characterize ticagrelor exposure-response relationship for platelet inhibition in patients with stable coronary artery disease (CAD) and a history of myocardial infarction (MI), using nonlinear mixed effects modelling and simulation. METHODS: Platelet function data were integrated with plasma concentration data of …

nl, jp, se, us, pl, gb (code pays fourni par la source)

Model selection and averaging of nonlinear mixed-effect models for robust phase III dose selection

Yasunori Aoki, Daniel Röshammar, Bengt Hamrén, Andrew C. Hooker

Population model-based (pharmacometric) approaches are widely used for the analyses of phase IIb clinical trial data to increase the accuracy of the dose selection for phase III clinical trials. On the other hand, if the analysis is based on one selected model, …

se, jp (code pays fourni par la source)