Population Pharmacokinetics and Pharmacodynamics of GSK961081 (Batefenterol), a Muscarinic Antagonist and β2-Agonist, in Moderate-to-Severe COPD Patients: Substudy of a Randomized Trial
| Autor: | John H. Riley, Pascal Wielders, Robert Chan, Claire Ambery, Andrea Ludwig-Sengpiel |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Adult
Male Drug media_common.quotation_subject Muscarinic Antagonists Quinolones Pharmacology law.invention Pulmonary Disease Chronic Obstructive Pharmacotherapy Double-Blind Method Randomized controlled trial law Forced Expiratory Volume Humans Medicine Original Research Article Adrenergic beta-2 Receptor Agonists Aged media_common COPD Dose-Response Relationship Drug business.industry Batefenterol Muscarinic antagonist Middle Aged medicine.disease Dose–response relationship Pharmacodynamics Female Carbamates business medicine.drug |
| Zdroj: | Drugs in R&D |
| ISSN: | 1174-5886 |
| DOI: | 10.1007/s40268-015-0104-x |
| Popis: | GSK961081 (batefenterol) is a novel bifunctional molecule composed of a muscarinic antagonist and a β2-agonist. The aims of this substudy were (1) to characterize the population pharmacokinetics (PK) and pharmacodynamics (PD) of GSK961081 in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD); and (2) to investigate the relationship between systemic exposure to GSK961081 and key cardiac-related safety parameters. Three once-daily doses (100, 400, and 800 μg) and three twice-daily doses (100, 200, and 400 μg) of GSK961081 DISKUS were investigated. A two-compartment disposition PK model with first-order absorption adequately described the plasma GSK961081 concentration-time data. An empirical maximum-effects PD model adequately described the forced expiratory volume in 1 s (FEV1) response relationship with the covariate baseline FEV1 on day 1. No clear relationships between GSK961081 plasma drug levels and cardiac-related safety parameters were apparent. The PK and PD models will be used to guide the dose selection and development of GSK961081 in patients with COPD. |
| Databáze: | OpenAIRE |
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