Assessment of respiratory function in safety pharmacology

Murphy, Dennis J.

doi:10.1046/j.1472-8206.2002.00060.x

Cited by 44 publications

(22 citation statements)

References 40 publications

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“…Subsequently, a lot of studies have been performed using head-out plethysmography for validation purposes and to test on adverse effects of chemicals and drugs, amongst others with inhalation exposure to allergens or bronchoconstricting agents (Neuhaus-Steinmetz et al, 2000; Glaab et al, 2001, 2002, 2005; Hoymann et al, 2009; Legaspi et al, 2010; Nirogi et al, 2012). Today, the head-out body plethysmography is a well-established and widely accepted technique which has been proven as a reliable method to measure pulmonary function (for reviews, see Murphy, 2002; Hoymann, 2006, 2007; Renninger, 2006; Glaab et al, 2007). …”

Section: Lung Function Measurement Techniques For Rodents – An Overviewmentioning

confidence: 99%

“…Changes in respiratory function can result either from alterations in the pumping apparatus including nervous and muscular components that controls the pattern of pulmonary ventilation or from changes in the mechanical properties of the gas exchange unit consisting of the lung with its associated airways, alveoli, and interstitial tissue (Murphy, 2002). Defects in pumping apparatus and reflex-related alterations can change the breathing pattern and are tested non-invasively in a conscious animal model.…”

Section: Introductionmentioning

confidence: 99%

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Lung Function Measurements in Rodents in Safety Pharmacology Studies

Hoymann¹

2012

Front. Pharmacol.

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The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step – as part of the “core battery” – lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a “follow-up study”. For these two stages of safety pharmacology testing, both non-invasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the non-invasive head-out body plethysmography and the invasive but repeatable body plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF50) or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g., EMEA Guideline 1/2008). It is concluded that both invasive and non-invasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies.

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Section: Lung Function Measurement Techniques For Rodents – An Overviewmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lung Function Measurements in Rodents in Safety Pharmacology Studies

Hoymann¹

2012

Front. Pharmacol.

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“…The techniques and procedures for measuring respiratory function parameters are well established in guinea pigs, rats, and dogs. 20 The index for respiratory system safety pharmacology evaluations is given in Table 7.3 .…”

Section: Respiratory Systemmentioning

confidence: 99%

Safety Pharmacology and Toxicity Study of Herbal Medicines

Jing-yu

Wei

Liu³

2010

Traditional Herbal Medicine Research Methods

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“…Some focus for in vitro assays relevant to respiratory SP can be identified by considering those aspects of in vivo respiratory physiology and pharmacology that one would not want to be affected by a potential new drug (for review see [23]). For example, it would be a concern if a compound decreased lung resistance, lung compliance or mucociliary clearance; interference with either efferent or afferent airway nerve traffic also would not be desirable.…”

Section: Implementation Of In Vitro Systemsmentioning

confidence: 99%

The application of in vitro methods to safety pharmacology

Wakefield

Pollard

Redfern

et al. 2002

Fundamemntal Clinical Pharma

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The ICH S7A guideline defines safety pharmacology (SP) studies as those that investigate 'the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above', and permits both in vivo and in vitro techniques, as appropriate. The implementation of these ICH guidelines by the pharmaceutical industry--whilst providing a welcome and long overdue clarity into the scientific rationale, timing and regulatory requirements for SP studies--has also generated new challenges, both logistical and scientific, which have a major impact on drug development. These factors have motivated us to consider the introduction of in vitro techniques at an early stage of SP evaluation. Amongst these factors are: the expanded range of study types and physiological parameters to be assessed, the increased 'front-loading' of SP at earlier stages of the drug discovery process; the greater number of new chemical entities (NCEs) to be tested, together with limited compound supply; the condensed time frames for drug development, the higher and quicker throughput of in vitro vs. in vivo tests; the increasing predictability of in vitro tests and application of the '3Rs' rule of animal welfare (reduction, replacement and refinement). Also, there is the failure of traditional in vivo safety evaluation to predict certain clinical side-effects. The use of molecular (e.g. fluorescence and cloned ion channel), cellular (e.g. patch clamp and isolated cardiac cells) and tissue-based (e.g. microelectrodes and Purkinje fibres) methods offers a wide portfolio of novel techniques for SP evaluation of NCEs at a pre-in vivo stage. Thus, innovative in vitro techniques will contribute significantly to the early SP evaluation of NCEs.

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Assessment of respiratory function in safety pharmacology

Cited by 44 publications

References 40 publications

Lung Function Measurements in Rodents in Safety Pharmacology Studies

Lung Function Measurements in Rodents in Safety Pharmacology Studies

Safety Pharmacology and Toxicity Study of Herbal Medicines

The application of in vitro methods to safety pharmacology

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