A novel propellant-free inhalation drug delivery system for cardiovascular drug safety evaluation in conscious dogs

Journal of Pharmacological and Toxicological Methods
Michael MarkertBrian Guth

Abstract

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. 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 x 4 Latin square design. Three doses of Formoterol (0.6, 1.2, and 2.4 microg/kg, dissolved in 60% ethanol) were administered by inhalation together with a vehicle (60% ethanol) treatment by applying three inhalations, each consisting of 10 microl solution. 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. Drug administration by inhalation in the conscious labrador dog using the Respimat is a useful new model for safety pharmacology studi...Continue Reading

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Citations

Jun 24, 2010·Journal of Pharmacological and Toxicological Methods·A SivarajahN Edmunds
May 12, 2009·Journal of Pharmacological and Toxicological Methods·Michael MarkertBrian Guth
Apr 25, 2008·Journal of Pharmacological and Toxicological Methods·Miriam StubhanBrian Guth
Jun 23, 2007·Journal of Pharmacological and Toxicological Methods·Michael MarkertBrian Guth
May 30, 2006·Journal of Pharmacological and Toxicological Methods·Anja KlumppBrian Guth
May 28, 2009·Journal of Pharmacological and Toxicological Methods·B D GuthJ-P Valentin
May 5, 2012·Journal of Pharmacological and Toxicological Methods·Michael MarkertBrian Guth
Feb 19, 2009·Antonie van Leeuwenhoek·Yan Zhong Li, Zhi Biao Nan

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