Back to Search
Start Over
A novel propellant-free inhalation drug delivery system for cardiovascular drug safety evaluation in conscious dogs
- Source :
-
Journal of Pharmacological & Toxicological Methods . Sep2004, Vol. 50 Issue 2, p109-119. 11p. - Publication Year :
- 2004
-
Abstract
- Introduction: Estimation of possible cardiovascular side effects belongs to the safety assessment of every drug candidate. This paper describes a new strategy for treating conscious labrador dogs with drugs by inhalation using a specially designed mask and a novel inhaler device. Methods: Labrador dogs (male or female) were used that had transducers implanted for the measurement of left ventricular and descending aortic blood pressures and an ECG for use together with a telemetry system. Administration by inhalation was achieved using a novel delivery device. The Respimat device is a propellant-free inhaler to deliver aerosols from solutions. The new system was evaluated using Formoterol with four dogs using a 4×4 Latin square design. Three doses of Formoterol (0.6, 1.2, and 2.4 μg/kg, dissolved in 60% ethanol) were administered by inhalation together with a vehicle (60% ethanol) treatment by applying three inhalations, each consisting of 10 μl solution. Results: Formoterol increased HR, QRS-interval, QT-interval, and LVPdP/dtmax and dose-dependently decreased systolic and diastolic BP. This effect lasted up to 14 h. Discussion: Drug administration by inhalation in the conscious labrador dog using the Respimat is a useful new model for safety pharmacology studies of new drug candidates that are intended to be given by inhalation in the clinic. [Copyright &y& Elsevier]
- Subjects :
- *CARDIOVASCULAR agents
*AEROSOLS
*PHARMACOLOGY
*LABRADOR retriever
Subjects
Details
- Language :
- English
- ISSN :
- 10568719
- Volume :
- 50
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Pharmacological & Toxicological Methods
- Publication Type :
- Academic Journal
- Accession number :
- 14512929
- Full Text :
- https://doi.org/10.1016/j.vascn.2004.03.006