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June 3, 2020 / in Scientific Article

Abstract

Introduction

A number of drugs in clinical trials are discontinued due to potentially life-threatening airway obstruction. As some drugs may not cause changes in core battery parameters such as tidal volume (Vt), respiratory rate (RR) or minute ventilation (MV), including measurements of respiratory mechanics in safety pharmacology studies represents an opportunity for design refinement. The present study aimed to test a novel non-invasive methodology to concomitantly measure respiratory system resistance (Rrs) and conventional respiratory parameters (Vt, RR, MV) in conscious Beagle dogs and cynomolgus monkeys.

Methods

An Airwave Oscillometry system (tremoFlo; THORASYS Inc., Montreal, Canada) was used to concomitantly assess Rrs and conventional respiratory parameters before and after intravenous treatment with a bronchoactive agent. Respiratory mechanics measurements were performed by applying a short (i.e. 16 s) single high frequency (19 Hz) waveform at the subject's airway opening via a face mask. During measurements, pressure and flow signals were recorded. After collection of baseline measurements, methacholine was administered intravenously to Beagle dogs (n = 6) and cynomolgus monkeys (n = 4) at 8 and 68 μg/kg, respectively.

Results

In dogs, methacholine induced significant increases in Vt, RR and MV while in monkeys, it only augmented RR. A significant increase in Rrs was observed after methacholine administration in both species with mean percentage peak increases from baseline of 88 (53)% for dogs and 28 (16)% for cynomolgus monkeys.

Conclusion

Airwave Oscillometry appears to be a promising non-invasive methodology to enable respiratory mechanics measurements in conscious large animals, a valuable refinement in respiratory safety pharmacology.

The articles include uses of tremoflo products or describes research devices that may not have been cleared by FDA
Keywords
airway resistance, Airwave oscillometry, Dog, Methacholine, Monkey, Respiratory, Safety pharmacology
Source

Bassett L, Troncy E, Robichaud A, Schuessler TF, Pouliot M, Ascah A, et al. Non-invasive measure of respiratory mechanics and conventional respiratory parameters in conscious large animals by high frequency Airwave Oscillometry. J Pharmacol Toxicol Methods [Internet]. 2014 [cited 2014 Jul 30];70(1):62–5

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