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Biomedical subjects

J N Pritchard

Publications and source records attributed to J N Pritchard.

9 recordsLinked to original sources
PubMed2001

The influence of lung deposition on clinical response.

Delivery of more drug to the lung may appear to be a desirable goal in the treatment of asthma and chronic obstructive pulmonary disease, since only 10 to 15% of a drug dose administered via a metered dose inhaler (MDI) reaches the lung. However, increasing the dose of most inhaled drugs may only lead to an increase in side effects, since maximal clinical benefit is usually obtained with the currently recommended dosages. Improving the regional deposition of inhaled drugs may be a more effective way of modifying clinical response. Particle size is the most significant determinant of the deposition pattern of inhaled drugs. Optimum drug delivery to the conducting airways occurs with particles ranging from 2.5 to 6 microm; particles <2.5 microm are deposited mainly in the alveoli where they may exert no pharmacodynamic effect and are rapidly absorbed, increasing the risk of systemic adverse events. Delivery devices can be compared by estimating the lung and systemic exposures, taking into account the efficacy and safety dose-response relationships for the drug-device combination. Current devices have profoundly different lung deposition profiles that could affect clinical efficacy when switching devices. Devices that achieve a high lung to systemic ratio for the inhaled drug are preferable.

Administration, Inhalation↗
PubMed1989

Dust overloading causes impairment of pulmonary clearance: evidence from rats and humans.

There is increasing evidence, principally from experiments involving diesel exhaust particles, that pulmonary clearance becomes impaired after exposure to high dust concentrations. This effect is discussed here as a function of the exposure methodology as well as dust concentration. Metal oxide particles do not demonstrate this effect until higher exposures, presumably due to some solubility. Limited data suggesting impaired clearance at high dust loadings in humans is discussed. Thus, impairment may affect all materials and species if deposited in the lung at sufficient rates.

Animals↗
PubMed1989

Dosimetric equivalence of tar deposition in rodents and man.

It has proved very difficult to produce cancer in laboratory animals following the inhalation of tar from cigarette smoke. Amongst other factors, this may be due to the dose that animals get in comparison to humans. Data reported here suggest that the average dose to the bronchial region of the lung, estimated using radiotracer techniques, may be a factor of 4 lower. The local dose to the carinal is also discussed; this may be lower still.

Administration, Inhalation↗
PubMed1985

The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillation.

A comparison was made of the distribution of dust in the rat lung following its administration by inhalation and by a single intratracheal instillation. Due to the wide variety of instillation techniques, an "average" method was adopted based on the results from a survey of 15 laboratories in Europe and the USA. Novel techniques were developed to quantify the distribution of dust within the lung both microscopically and macroscopically. The distribution of dust obtained by instillation was shown to be much less homogeneous that that obtained by inhalation and penetration to the periphery was minimal. The effects of (a) changing the volume of suspension, (b) changing the concentration of the suspension, and (c) introducing air into the syringe were investigated. Although the use of air in the syringe was beneficial, none of the other modifications effected any improvement in the distribution. The difference in distribution following inhalation and instillation leads to the conclusion that the latter may be of use in establishing the nature and comparative response of the lung to different dusts, but not for establishing an absolute dose-response relationship. It is recommended that no more than 1 mg of fibrous or 5 mg of nonfibrous dust be given in a single instillation to adult rats.

Animals↗
PubMed1983

Alveolar deposition of sized particles of 239PuO2 in the mouse.

Data on the alveolar deposition of 239PuO2 particles in the mouse are presented. It is shown that alveolar deposition falls with increasing activity median aerodynamic diameter (AMAD) over the range 0.6 to 2.4 microns. In the mouse, any peak in alveolar deposition must occur at an AMAD of less than 1 micron. Information is also provided on the relative lobar concentrations (RLCs) of 239PuO2. The RLC is greatest in the right apical lobe and increases quite sharply with AMAD. The RLCs of the other lobes of the right lung decline with AMAD. The RLC in the left lobe is relatively unaffected by AMAD.

Aerosols↗