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Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study.
- Source :
-
International journal of chronic obstructive pulmonary disease [Int J Chron Obstruct Pulmon Dis] 2013; Vol. 8, pp. 159-67. Date of Electronic Publication: 2013 Mar 27. - Publication Year :
- 2013
-
Abstract
- Background: The combination of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a selective long-acting β₂ agonist, is in development for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the pharmacokinetics, safety and tolerability, and pharmacodynamics of once-daily, inhaled UMEC and UMEC/VI when co-administered with oral verapamil, a moderate P-glycoprotein transporter and moderate cytochrome P450 3A4 (CYP3A4) inhibitor frequently used by patients with COPD and cardiovascular comorbidities.<br />Methods: Subjects were randomized to one of two 13-day treatment regimens: UMEC 500 μg or UMEC 500 μg/VI 25 μg. All subjects received a single tablet containing 240 mg verapamil on each of days 9-13.<br />Results: Repeat doses of UMEC and UMEC/VI in combination with and without verapamil were safe and well tolerated. There was no increase in systemic exposure of UMEC when administered in combination with VI compared to UMEC alone. UMEC maximum concentration was similar with or without verapamil; a moderate increase in UMEC area under the curve (approximately 1.4-fold) was observed with verapamil. Verapamil did not increase systemic exposure to VI following administration of the UMEC/VI combination.<br />Conclusion: Administration of UMEC and UMEC/VI combination was well tolerated and did not show clinically relevant increases in systemic exposure for either drug. The UMEC/VI combination is unlikely to have a clinically meaningful drug-drug interaction with moderate P-glycoprotein transporter and CYP3A4 inhibitor drugs.
- Subjects :
- Administration, Oral
Adolescent
Adrenergic beta-2 Receptor Agonists blood
Adult
Aged
Benzyl Alcohols blood
Chlorobenzenes blood
Drug Combinations
Dry Powder Inhalers
Female
Heart Rate
Humans
Male
Middle Aged
Muscarinic Antagonists blood
Potassium blood
Quinuclidines blood
Vasodilator Agents blood
Verapamil blood
Young Adult
Adrenergic beta-2 Receptor Agonists therapeutic use
Benzyl Alcohols therapeutic use
Chlorobenzenes therapeutic use
Muscarinic Antagonists therapeutic use
Pulmonary Disease, Chronic Obstructive drug therapy
Quinuclidines therapeutic use
Vasodilator Agents therapeutic use
Verapamil therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1178-2005
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- International journal of chronic obstructive pulmonary disease
- Publication Type :
- Academic Journal
- Accession number :
- 23569370
- Full Text :
- https://doi.org/10.2147/COPD.S40859