Pharmacokinetics and safety of a single dose of the novel LAMA/LABA fixed-dose combination of glycopyrronium/formoterol fumarate dihydrate metered dose inhaler, formulated using co-suspension delivery technology, in Japanese healthy subjects
| Autor: | Joel Miller, Colin Reisner, Shahid Siddiqui, Paolo DePetrillo, Andrea Maes, Ubaldo J. Martin |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine Adolescent Fixed-dose combination Cmax Muscarinic Antagonists Pharmacology Young Adult 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Double-Blind Method Japan Suspensions Pharmacokinetics Formoterol Fumarate Administration Inhalation medicine Humans Pharmacology (medical) Metered Dose Inhalers 030212 general & internal medicine Cross-Over Studies Dose-Response Relationship Drug integumentary system business.industry Biochemistry (medical) Area under the curve Muscarinic antagonist Middle Aged Glycopyrrolate Metered-dose inhaler Crossover study Bronchodilator Agents Drug Combinations 030228 respiratory system Area Under Curve Female Formoterol business medicine.drug |
| Zdroj: | Pulmonary Pharmacology & Therapeutics. 53:33-38 |
| ISSN: | 1094-5539 |
| DOI: | 10.1016/j.pupt.2018.09.005 |
| Popis: | Background Chronic obstructive pulmonary disease (COPD) causes significant mortality in Japan. GFF MDI is a long-acting muscarinic antagonist/long-acting β 2 -agonist fixed-dose combination of glycopyrronium (GP) and formoterol fumarate dihydrate (FF), delivered by a metered dose inhaler (MDI) using co-suspension delivery technology, for the long-term maintenance treatment of COPD. Methods This randomized, Phase I, single-dose, four-treatment, four-period, crossover study (NCT02196714) examined the pharmacokinetic (PK) and safety profile of two doses of GFF MDI (28.8 μg/10 μg and 14.4 μg/10 μg) and two doses of GP MDI (28.8 μg and 14.4 μg), both formulated using co-suspension delivery technology, in healthy Japanese subjects (18–45 years of age). PK parameters included area under the curve (AUC) from 0 to 12 h (AUC 0–12), AUC from 0 to the time of the last measurable plasma concentration, maximum observed plasma concentration (Cmax), and time to Cmax. Safety was monitored throughout the study. Results Plasma GP profiles were comparable between GFF MDI and GP MDI formulations containing the same GP dose. Increases in GP AUC0–12 and Cmax were generally dose proportional from 14.4 to 28.8 μg after administration of either formulation. Conclusions The addition of FF 10 μg to GP MDI 28.8 μg or 14.4 μg in a fixed-dose combination did not appreciably alter the PK of GP, nor did an increase in GP dose from 14.4 μg to 28.8 μg in a fixed-dose combination with FF 10 μg appreciably alter the PK of formoterol . Both formulations of GFF MDI and GP MDI were well tolerated in healthy Japanese subjects. Data from this study support further evaluation of GFF MDI in Japanese patients with COPD. |
| Databáze: | OpenAIRE |
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