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

Publication ,  Journal Article
Noveck, RJ; Douglas, PS; Chow, S-C; Mangum, B; Kori, S; Kellerman, DJ
Published in: Drug Des Devel Ther
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.

Duke Scholars

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Published In

Drug Des Devel Ther

DOI

EISSN

1177-8881

Publication Date

2013

Volume

7

Start / End Page

619 / 625

Location

New Zealand

Related Subject Headings

  • Systole
  • Pulmonary Artery
  • Migraine Disorders
  • Middle Aged
  • Metered Dose Inhalers
  • Male
  • Humans
  • Female
  • Echocardiography
  • Double-Blind Method
 

Citation

APA
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ICMJE
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Noveck, R. J., Douglas, P. S., Chow, S.-C., Mangum, B., Kori, S., & Kellerman, D. J. (2013). Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine. Drug Des Devel Ther, 7, 619–625. https://doi.org/10.2147/DDDT.S44093
Noveck, Robert J., Pamela S. Douglas, Shein-Chung Chow, Barry Mangum, Shashidhar Kori, and Donald J. Kellerman. “Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.Drug Des Devel Ther 7 (2013): 619–25. https://doi.org/10.2147/DDDT.S44093.
Noveck, Robert J., et al. “Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine.Drug Des Devel Ther, vol. 7, 2013, pp. 619–25. Pubmed, doi:10.2147/DDDT.S44093.

Published In

Drug Des Devel Ther

DOI

EISSN

1177-8881

Publication Date

2013

Volume

7

Start / End Page

619 / 625

Location

New Zealand

Related Subject Headings

  • Systole
  • Pulmonary Artery
  • Migraine Disorders
  • Middle Aged
  • Metered Dose Inhalers
  • Male
  • Humans
  • Female
  • Echocardiography
  • Double-Blind Method