Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.

Noveck, Robert J

Douglas, Pamela S

Chow, Shein-Chung

Mangum, Barry

Kori, Shashidhar

Kellerman, Donald J

New Zealand

2015-12-15T16:21:19Z

2013

OBJECTIVE: MAP0004 is an investigational product which delivers dihydroergotamine (DHE) through the lung via a breath-synchronized metered dose inhaler. The objective of this study was to compare the acute effects of orally inhaled and intravenous (IV) DHE to placebo on maximum change and area under the curve for pulmonary arterial systolic pressure (PASP). RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo-controlled, 3-period, crossover study of 24 health adults. Trial registration NCT01089062. Study assessments included pharmacokinetics, electrocardiograms (ECG), and validated echocardiographic (Doppler)-derived measures of PASP by echocardiogram. The primary endpoint was the absolute change in calculated PASP using area under the curve, 0 to 2 hours (AUC(0-2h)). RESULTS: The change in PASP with IV DHE was significantly different than MAP0004 and placebo (AUC(0-2h)2857, 2624, and 2453 mmHg*min, respectively). After a second dose of MAP0004, AUC(0-4h) remained lower with MAP0004 than with a single dose of IV DHE. Adverse events were more common with IV DHE than with MAP0004 or placebo. None of the treatments produced clinically significant changes in PASP or other cardiac parameters. Changes in PASP were significantly smaller with MAP0004 compared with IV DHE. CONCLUSION: These results indicate the effects 1 mg of orally inhaled DHE on the cardiovascular system are less than with 1 mg of IV DHE, and that serial echocardiography can be a useful noninvasive means of assessing acute systemic effects.

http://www.ncbi.nlm.nih.gov/pubmed/23926420

dddt-7-619

1177-8881

https://hdl.handle.net/10161/11172

eng

Informa UK Limited

Drug Des Devel Ther

10.2147/DDDT.S44093

MAP0004

dihydroergotamine

echo

echocardiogram

inhaled

intravenous

pulmonary artery systolic pressure

Administration, Inhalation

Administration, Intravenous

Adolescent

Adult

Cross-Over Studies

Dihydroergotamine

Double-Blind Method

Echocardiography

Female

Humans

Male

Metered Dose Inhalers

Middle Aged

Migraine Disorders

Pulmonary Artery

Systole

Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.

Journal article

Douglas, Pamela S|0000-0001-9876-4049

http://www.ncbi.nlm.nih.gov/pubmed/23926420

619

625

Basic Science Departments

Biostatistics & Bioinformatics

Clinical Science Departments

Duke

Duke Clinical Research Institute

Faculty

Institutes and Centers

Medicine

Medicine, Cardiology

School of Medicine

Staff

Published online

7