The novel elastase inhibitor BAY 85-8501: Bioavailability and Food effect study to evaluate pharmacokinetics of tablet formulations
J. Nagelschmitz, M. Becka, D. Kaufel, S. Schwers, G. Wensing (Wuppertal, Germany)
Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs
Session: New treatments for cough, asthma, COPD and ILDs
Session type: Poster Discussion
Number: 1511
Disease area: Airway diseases
Abstract Human neutrophil elastase (HNE) is a key mediator of tissue remodeling and inflammation. An excess of HNE activity has been implicated in the pathogenesis of inflammatory pulmonary diseases, e.g. bronchiectasis, COPD and pulmonary hypertension. HNE inhibitors could potentially restore the protease/anti-protease balance in these diseases providing a new therapeutic option.BAY 85-8501 is a novel, selective and reversible HNE inhibitor with activity in the picomolar concentration range, which reveals target inhibition in the lung and ameliorates pulmonary inflammation in preclinical models.Relative bioavailability of 0.1 and 0.5 mg BAY 85-8501 immediate release tablets (tbl) and influence of concomitant food intake on 0.5 mg tbl was investigated in a 4-fold crossover study in 12 healthy male subjects. Treatments were single doses of tbl 0.1 and 0.5 and oral liquid 0.5 mg fasted and tbl 0.5 mg with food.All treatments were safe and well tolerated, no changes of clinical safety (BP, HR, ECG) and clinical laboratory parameters occurred.Tablet formulations of 0.5 and 0.1 mg revealed a comparable dose-normalized exposure, however, absorption rate was nearly halved for the tablet. Intake of American breakfast reduced the absorption rate (max. concentration (40 %) reached after 4 h), but not its extent. Terminal half-life after 0.5 mg ranged from 110 to 121 h.Bioavailability in terms of AUC was comparable between solution and tablet. Food intake decreased absorption rate, but not absorption extent. Tablets have favorable PK and are safe for further treatment in clinical studies.
Rating:
You must login to grade this presentation.
Share or cite this content
Citations should be made in the following way:
J. Nagelschmitz, M. Becka, D. Kaufel, S. Schwers, G. Wensing (Wuppertal, Germany). The novel elastase inhibitor BAY 85-8501: Bioavailability and Food effect study to evaluate pharmacokinetics of tablet formulations. Eur Respir J 2014; 44: Suppl. 58, 1511
You must login to share this Presentation/Article on Twitter, Facebook, LinkedIn or by email.
Member's Comments
Related content which might interest you:
Related content which might interest you:
The novel elastase inhibitor BAY 85-8501: First-in-man study to evaluate safety, tolerability and pharmacokinetics in healthy male subjects Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs Year: 2014
Safety, tolerability and pharmacokinetics of a new inhaled once-daily phosphodiesterase (PDE) 4 inhibitor in healthy volunteers Source: Annual Congress 2013 –Novel drugs and biomarkers in respiratory medicine Year: 2013
Effect of the CYP3A4 inhibitor ketoconazole on the pharmacokinetics and pharmacodynamics of AZD5069, an oral CXCR2 antagonist Source: International Congress 2014 – Novel evidence relating to respiratory treatment development Year: 2014
The novel elastase inhibitor BAY 85-8501 provides a new approach in the treatment of pulmonary diseases Source: International Congress 2014 – New drugs for asthma, COPD and pulmonary fibrosis Year: 2014
In vitro profile of the new inhaled pan-JAK inhibitor LAS194046Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs Year: 2014
Bronchoprotective activity and safety assessment of two novel dual-acting MABA compounds (LAS190792 and LAS191351) in dogs Source: International Congress 2014 – Novel targets and drugs for asthma and COPD Year: 2014
In vivo efficacy of CHF6001, an inhaled PDE4 inhibitor with a wide therapeutic window Source: International Congress 2014 – Animal models in respiratory drug development Year: 2014
Safety, tolerability and pharmacokinetics of CHF 6001, a novel selective inhaled PDE4 inhibitor, in healthy volunteers Source: International Congress 2016 – Preclinical pharmacology: drug targets and mechanisms of action Year: 2016
In vitro characterization of a novel inhaled PI3Kd inhibitor LAS194223Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs Year: 2014
Effect of the combination of doxofylline and montelukast on LPS-induced leukocyte migration to the lung Source: International Congress 2014 – Animal models in respiratory drug development Year: 2014
Safety, immunogenicity and pharmacokinetics (PK) of a 120 mg/kg/week dose of alpha1 -proteinase inhibitor in alpha1 -antitrypsin deficiency Source: Annual Congress 2013 –COPD drugs: new findings Year: 2013
Pharmacokinetics (PK), safety and tolerability of abediterol and mometasone furoate fixed- and free-dose combinations in healthy subjects Source: International Congress 2014 – Novel approaches and evidence for drug development in respiratory diseases Year: 2014
Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single (SD) and repeat (RD) inhaled doses of a novel phosphoinositide 3-kinase δ inhibitor (PI3Kδ), GSK2269557, administered to healthy smokers Source: International Congress 2014 – New drugs for asthma, COPD and pulmonary fibrosis Year: 2014
Therapeutic potential of CPL-407-105 – Novel potent JAK/STAT pathway inhibitor for the treatment of asthma Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs Year: 2014
Safety, tolerability and pharmacokinetics of an oral competitive reversible CRTh2 antagonist, QAW039, in healthy subjects Source: International Congress 2014 – Allergy and asthma: novel findings based on human cell biology Year: 2014
LATE-BREAKING ABSTRACT: Safety, pharmacokinetics and pharmacodynamics of BI 1060469, a novel oral CRTH2 antagonist Source: International Congress 2016 – Asthma management Year: 2016
Safety and pharmacokinetics study of a single ascending dose of C16TR for inhalation (INS1009) Source: International Congress 2016 – Pulmonary hypertension: the clinic II Year: 2016
Systemic exposure and lung bioavailability across two different dose strengths of CHF5993 a novel Triple pMDI Source: International Congress 2016 – Pulmonary drug delivery Year: 2016
Preclinical characterization of CPL-302-201, a novel, highly potent and selective PI3Kδ inhibitor for the treatment of inflammatory disorders Source: International Congress 2014 – New treatments for cough, asthma, COPD and ILDs Year: 2014
Safety, tolerability and pharmacokinetics of QAV680, an oral CRTh2 antagonist, in healthy subjects Source: International Congress 2014 – Allergy and asthma: novel findings based on human cell biology Year: 2014