A5083860568- Complement system in diseases
- Sleep and Wakefulness Research
- Breastfeeding Practices and Influences
- Pharmaceutical studies and practices
- Platelet Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Blood disorders and treatments
- Innovative Microfluidic and Catalytic Techniques Innovation
- Sleep and related disorders
- Drug Transport and Resistance Mechanisms
- Adrenal Hormones and Disorders
- Microfluidic and Capillary Electrophoresis Applications
- Infant Nutrition and Health
- Antibiotics Pharmacokinetics and Efficacy
- Electrowetting and Microfluidic Technologies
- Lipid Membrane Structure and Behavior
- Circadian rhythm and melatonin
- Neuroscience of respiration and sleep
- Pharmacogenetics and Drug Metabolism
- Cardiac electrophysiology and arrhythmias
- Receptor Mechanisms and Signaling
- Pharmacological Effects and Toxicity Studies
- SARS-CoV-2 and COVID-19 Research
- Analytical Chemistry and Chromatography
- Neuroscience and Neuropharmacology Research
Idorsia (Switzerland)
2020-2024
University of Basel
2020-2024
University Children’s Hospital Basel
2020-2024
Idera Pharmaceuticals (United States)
2024
ETH Zurich
2020-2021
Idiap Research Institute
2020
Aims The orexin system is involved in anxiety behaviour and corresponding physiological reactions constitutes a target for treatment of disorders. ACT‐539313 potent, selective orexin‐1 receptor antagonist being developed the This first‐in‐human study investigated its single‐dose pharmacokinetics (PK) including food effect, pharmacodynamics (PD), safety tolerability. Methods double‐blind, placebo‐controlled, randomized included 40 healthy male subjects. Ascending oral doses 10–400 mg were 5...
The novel dual orexin receptor antagonist daridorexant was approved in 2022 for the treatment of adult patients with insomnia. aim this post-marketing study to measure and its major metabolites breast milk plasma 10 healthy lactating subjects. This single-center, open-label evaluated transfer analytes into milk. A single dose 50 mg orally administered morning. Milk blood samples were collected pre-dose over a period 72 h after dosing. pharmacokinetics assessed including cumulative amount...
Abstract In the field of bottom-up synthetic biology, lipid membranes are scaffold to create minimal cells and mimic reactions processes at or across membrane. this context, we employ here a versatile microfluidic platform that enables precise positioning nanoliter droplets with user-specified compositions in defined pattern. Adjacent make contact form droplet interface bilayer simulate cellular membranes. Translocation molecules tailored by addition alpha-hemolysin selected droplets....
We investigated the permeation of molecules across lipid membranes on an open microfluidic platform. An array droplet pairs was created by spotting aqueous droplets, dispersed in a oil solution, onto plate with cavities surrounded hydrophobic substrate. Droplets two adjacent come contact and form artificial bilayer, called interface bilayer (DIB). The method allows for monitoring fluorescently tagged compounds from donor to acceptor droplet. A mathematical model applied describe kinetics...
Aberrantly controlled activation of the complement system contributes to inflammatory diseases. Safety, tolerability, and pharmacokinetics single-ascending doses ACT-1014-6470, a novel orally available factor 5a receptor 1 antagonist, were assessed in randomized, double-blind, placebo-controlled Phase study. Six ACT-1014-6470 (0.5-200 mg) selected after predictions from Complex Dedrick plot. In each group, or matching placebo was administered six two healthy male individuals under fed...
ACT-1014-6470 is an orally available complement factor 5a receptor 1 antagonist and a novel treatment option in auto-inflammatory diseases. The vitro inhibition potential of on cytochrome P450 isozymes (CYPs) its effect the pharmacokinetics (PK) CYP2C19 CYP3A4 substrates omeprazole midazolam, respectively, humans were assessed. In assays conducted with isoform-specific human liver microsomes. open-label, two-period, fixed-sequence cocktail study, single doses 20 mg 2 midazolam administered...
Targeting the complement factor 5a receptor 1 (C5a1 receptor) offers potential to treat various autoimmune diseases. The C5a1 antagonist ACT-1014-6470 was well tolerated in a single-ascending dose study healthy subjects. This double-blind, randomized, placebo-controlled aimed investigate safety, tolerability, pharmacokinetics (PK) and target engagement of multiple-ascending doses ACT-1014-6470.Per level, 10 male female subjects nonchildbearing (1:1 sex ratio) were enrolled assess 30, 60 120...
Abstract Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling challenging, alternative PK strategies are needed. In this case study we evaluated the suitability of saliva as matrix simplify studies infants, investigating metamizole, an analgesic used off‐label infants. Six and 6 sample collections were scheduled after single intravenous dose 10 mg/kg metamizole. Plasma/saliva pharmacometric (PMX) modeling active...
Abstract Introduction Daridorexant is a dual orexin receptor antagonist approved for the treatment of adult patients with insomnia. Following single-dose administration to healthy lactating female subjects, pharmacokinetics (PK) daridorexant and its major metabolites were assessed in breast milk plasma. Methods A single oral dose 50 mg was administered morning 10 subjects (fasted state). To evaluate transfer into milk, all secreted over 72 h post as well several plasma samples collected. The...
<h3>Introduction</h3> Pharmacokinetic (PK) studies in young children and infants are challenging, among others because of the invasiveness blood samples. Using saliva as matrix could increase their feasibility. A recent PK study prodrug metamizole (dipyrone), used off-label intravenous (i.v.) analgesic < 1 year age, aimed to assess its main metabolites after a single i.v. dose 10 mg/kg. It showed increased plasma exposure active metabolite 4-methylaminoantipyrine (MAA) four 3–12 months...
Abstract The novel oral complement factor 5a receptor 1 antagonist ACT‐1014‐6470 was well tolerated in single‐ and multiple‐ascending dose studies, including 24 h Holter electrocardiogram (ECG) recordings evaluating its cardiodynamics based on data from single doses of 30–200 mg twice‐daily (b.i.d.) dosing 30–120 for 4.5 days. By‐time point, categorical, morphological analyses as concentration‐QT modeling simulations were performed. No relevant effect ECG parameters observed the categorical...