A5090466009- Inhalation and Respiratory Drug Delivery
- Computational Drug Discovery Methods
- Asthma and respiratory diseases
- Drug Solubulity and Delivery Systems
- Analytical Chemistry and Chromatography
- Advanced Chemical Sensor Technologies
- Pharmacogenetics and Drug Metabolism
- Biosimilars and Bioanalytical Methods
- Receptor Mechanisms and Signaling
- Machine Learning in Materials Science
- Crystallization and Solubility Studies
- Adipose Tissue and Metabolism
- Muscle Physiology and Disorders
- Heart Rate Variability and Autonomic Control
- Innovative Microfluidic and Catalytic Techniques Innovation
- Drug Transport and Resistance Mechanisms
- Pharmaceutical Economics and Policy
- Chronic Kidney Disease and Diabetes
- Antibiotics Pharmacokinetics and Efficacy
- Mitochondrial Function and Pathology
- Renal Diseases and Glomerulopathies
- Pharmacology and Obesity Treatment
- Protein purification and stability
- Pharmacological Effects and Assays
- Regulation of Appetite and Obesity
Boehringer Ingelheim (Germany)
2015-2025
Freie Universität Berlin
2015-2016
ABSTRACT A successful drug needs to combine several properties including high potency and good pharmacokinetic (PK) sustain efficacious plasma concentration over time. To estimate required doses for preclinical animal efficacy models or the clinics, in vivo PK studies need be conducted. Although prediction of ADME compounds using machine learning (ML) based on chemical structures is well established discovery, complete concentration–time profiles has only recently gained attention. In this...
ADME (Absorption, Distribution, Metabolism, Excretion) properties are key parameters to judge whether a drug candidate exhibits desired pharmacokinetic (PK) profile. In this study, we tested multi-task machine learning (ML) models predict and animal PK endpoints trained on in-house data generated at Boehringer Ingelheim. Models were evaluated both the design stage of compound (i. e., no experimental test compounds available) testing when particular assay would be conducted earlier assays may...
Aims Olodaterol, a novel β2‐adrenergic receptor agonist, is long‐acting, once‐daily inhaled bronchodilator approved for the treatment of chronic obstructive pulmonary disease. The aim present study was to describe plasma and urine pharmacokinetics olodaterol after intravenous administration oral inhalation in healthy volunteers by population pharmacokinetic modelling thereby infer its fate. Methods Plasma data (0.5–25 μg) (2.5–70 μg via Respimat® inhaler) were available from total 148...
ADME (Absorption, Distribution, Metabolism, Excretion) properties are key parameters to judge whether a drug candidate exhibits desired pharmacokinetic (PK) profile. In this study, we tested multi-task machine learning (ML) models predict and animal PK endpoints trained on in-house data generated at Boehringer Ingelheim. Models were evaluated both the design stage of compound (i.e., no experimental test compounds available) testing when particular assay would be conducted earlier assays may...
ABSTRACT A successful drug needs to combine several properties including high potency and good pharmacokinetic (PK) sustain efficacious plasma concentration over time. To estimate required doses for preclinical animal efficacy models or the clinics, in vivo PK studies need be conducted. While prediction of ADME compounds using Machine Learning (ML) based on chemical structures is well established discovery, complete concentration-time profiles has only recently gained attention. In this...
Olodaterol is an orally inhaled β2 -agonist for treatment of chronic obstructive pulmonary disease (COPD). The aims this population pharmacokinetic (PK) analysis were: (1) to investigate systemic PK and thereby make inferences about in asthmatic patients, COPD patients healthy volunteers, (2) assess whether differences efficacy might be expected based on characteristics.
Increasing affinity to lung tissue is an important strategy achieve pulmonary retention and prolong the duration of effect in lung. As a very heterogeneous organ, differences structure blood flow may influence local disposition. Here, novel preparation technique was employed investigate regional distribution four drugs (salmeterol, fluticasone propionate, linezolid, indomethacin) after intravenous administration rats. A semi-mechanistic model used describe observed drug concentrations...
The most suitable method for predicting the glomerular filtration rate (GFR) in obesity is currently debated. Therefore, multiple GFR/creatinine clearance prediction methods were applied to (morbidly) obese and nonobese patients ranging from moderate renal impairment hyperfiltration their predictions rated based on observed fosfomycin pharmacokinetics, as this model drug exclusively eliminated via filtration.The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of...
It is unclear whether mitochondrial dysfunction and redox stress contribute to impaired age-related muscle regenerative capacity. Here we characterized a novel compound, BI4500, that inhibits the release of reactive oxygen species (ROS) from quinone site in complex I (site IQ). We tested hypothesis ROS IQ contributes capacity aging muscle. Electron transfer system site-specific production was measured adult aged mouse isolated mitochondria permeabilized gastrocnemius fibers. BI4500 inhibited...
The fate of orally inhaled drugs is determined by pulmonary pharmacokinetic (PK) processes such as particle deposition, drug dissolution, and mucociliary clearance. Although each single process has been systematically investigated, a quantitative understanding on their interaction remains limited hence identifying optimal formulation characteristics for still challenging. To investigate this complex interplay, the can be integrated into mathematical models. However, existing modeling...
Abstract Background Treating pulmonary infections by administering drugs via oral inhalation represents an attractive alternative to usual routes of administration. However, the local concentrations after are typically not known and presumed benefits derived from experiences with specifically optimized for inhaled Objectives A physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was developed elucidate PK ciprofloxacin, rifampicin tigecycline link it bacterial PK/PD models....
ABSTRACT The suitability of a small molecule to become an oral drug is often assessed by simple physicochemical rules, the application ligand efficacy scores (combining properties with potency) or multi-parameter composite based on compound properties. These rules and are empirical typically lack mechanistic background, such as information pharmacokinetics (PK). We introduce new type Compound Quality Scores (specifically called dose-scores c max -scores), which explicitly include predicted...
Abstract Determining and understanding the target-site exposure in clinical studies remains challenging. This is especially true for oral drug inhalation local treatment, where identical to site of absorption, i.e., lungs. Modeling simulation based on pharmacokinetic (PK) data may be a valid approach infer pulmonary fate orally inhaled drugs, even without measurements. In this work, simulation-estimation study was systematically applied investigate five published model structures absorption....