21,227 Works

Influence of Aerosol Presentation on Lung Pathology Changes Induced in Rats

Graham Paul
Many inhaled drugs are developed as crystalline dry powder formulations for prolonged stability and to improve clinical control of drug delivery. Pre-clinical development of inhaled drugs consumes large masses of material, relative to other dose routes. Surrogate formulations or administration routes are sometimes proposed to expedite evaluation (first time) in humans. Such strategies defer the discharging of liabilities such as altered PK/PD or tolerability of the final (particulate) formulation until later in development.

Male rats were...

Head-out Plethysmography and Estimation of Inhaled Doses in Rats

Graham Paul
Non-clinical studies often report ‘doses’ calculated using an equation to estimate respired minute volume (RMV) from bodyweight, which may overlook habituation of animals to procedures. The influence of bodyweight development and procedural conditioning on the breath frequency (BF) and minute volume (MV) of rats was investigated over a 28-day treatment period (1-hour snout-only inhalation exposure). Rats were allowed to settle in restraint tubes for 15 minutes before aerosol administration; BF and MV were measured using...

Multivariate-based selection of drugs and implications of aerosol presentation for inhalation toxicology in rats

Graham Paul
Many inhaled drugs have been developed as crystalline dry powder formulations for prolonged stability and to optimise clinical drug delivery. Inhalation exposure of animals requires large masses of drug, relative to other dose routes in pre-clinical development. Surrogate formulations or administration routes are sometimes proposed to expedite early clinical evaluation. Such strategies defer discharging of liabilities such as altered pharmacokinetics-pharmacodynamics (PK/PD) or tolerability of the final formulation until later in development. Using three compounds of...

Capsule Based Aerosol Generation – test article conservation during the conduct of in vivo lead optimisation respiratory safety assessment studies

Simon Moore, Roger Goodway, Stuart Cracknell & Graham Paul
In both clinical and non-clinical settings, inhaled administration of drug substances to conscious subjects will typically require larger quantities of test article than any other routes of administration. This difference is greatest for dry powder formulations in which charge and 'proximity-related' effects are most pronounced. However, inefficiencies in the aerosol generation device and depletion of airborne particulates (e.g. sedimentation and impaction) in the delivery system are also contributory factors. Minimizing such losses, particularly when conducting...

Molecular and Physiological Analysis of Floral Signal Transduction

Ianis Matsoukas, Andrea Massiah & Brian Thomas
At a certain point in the plant life cycle annual plants undergo a major developmental transition and switch from vegetative to reproductive development. Physiological and genetic analysis of floral signal transduction has shown that floral induction time in most plant species is regulated by a combination of endogenous controls and environmental cues. The autonomous and gibberellin pathways promote floral induction in response to endogenous factors. The vernalization and photoperiod pathways promote flowering in response to...

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