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

详细信息    查看全文

• 作者：Markert ; Michael ; Klumpp ; Anja ; Trautmann ; Thomas ; Guth ; Brian
• 关键词：Methods ; Conscious labrador dog ; Respimat ; QT-interval ; By inhalation ; Long-acting β ; 2-adrenoceptor agonist
• 刊名：Journal of Pharmacological and Toxicological Methods
• 出版年：2004
• 出版时间：September - October, 2004
• 年：2004
• 卷：50
• 期：2
• 页码：109-119
• 全文大小：980 K

文摘

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.