Pulmonary deposition

TF Hatch, P Gross. Physical factors in respiratory deposition of aerosols. In Pulmonary Deposition and Retention of Inhaled Aerosols. New York Academic Press, 1964, pp. 27 43. 

M Vidgren, J Arppe, P Vidgren, P Vainio, M Silvasti, H Tukiainen. Pulmonary deposition of 99mTc-labelled salbutamol particles in healthy volunteers after inhalation from a metered-dose inhaler and from a novel multiple-dose powder inhaler. S.T.P. Pharm Sci 4 29-32, 1994. 

Oberdorster G. 1992. Pulmonary deposition, clearance and effects of inhaled soluble and insoluble cadmium compounds. In Nordberg GF, Herber RFM, Alessio L, eds. Cadmium in the human environment Toxicity and carcinogenicity. Lyon International Agency for Research on Cancer,... 

Hatch, T.F. and Gross, P. (1964). Pulmonary Deposition and Retention of Inhaled Aerosols. Academic Press, New York, pp. 16-17, 51-52, 147-168. 

Leong BKJ, Coombs JK, Sabaitis CP, Rop DA, Aaron CS (1998) Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats. J Appl Toxicol 18 149-160. 

Sweeney TD, Brain JD (1991) Pulmonary deposition determinants and measurement techniques. Toxicol Pathol 19 384—397. 

In relation to the above it is obvious that passage of the pulmonary epithelium may depend on characteristics of a drug molecule. Not only the size, but also its solubility, overall charge, structural conformation and potential aggregation can have a significant effect on the absorption rate and bioavailabUity of the drug after pulmonary deposition. 

Gross, P., R. T. P. DeTreville, E. B. Tolker, M. Kaschak, and M. A. Babyak (1967). Experimental asbestosis the development of lung cancer in rats with pulmonary deposits of chrysotile dust. Arch. Environ. Health 15 343-355. 

Potentially toxic chemical species may be highly enriched in soluble forms on airborne particle surfaces. Such enrichments will have the greatest impact on the smallest, pulmonary-depositing particles with the highest surface area to volume ratios (11-14, 21, 22). Such a phenomenon is likely to occur for all particles produced by high temperature processes, both anthropogenic and natural (11-14). 

In contrast, a decreasing proportion of particles from 1 p (100%) up to lOp (1%) reaches the pulmonary region in the human lung during normal breathing via the nose. Once there, maximum pulmonary deposition occurs for particle sizes of l-4p about 25% of Ip, 35% of2p, 30% of 3p, and 25% of4p. °... 

Elo R, Maatta K, Uksila E, Arstila AU Pulmonary deposits of titanium dioxide in man. Arch Pathol 94 417-424, 1972... 

Kodama Y, Ishimatsu S, Matsuno K, et al. 1985a. Pulmonary deposition and clearance of a nickel oxide aerosol by inhalation. Biol Trace Elem Res 7 1-8. 

Industrial processes, such as mUling and mining, construction work, and the burning of wood or fossil fuel, generate particulates that can be directly toxic or can serve as vectors for the transfer of bound material, such as sulfuric acid, metals, and hydrocarbons, into the lungs. Natural products such as pollen, anthrax spores, and animal dander can elicit toxic reactions on inhalation or skin contact. The inhalation of asbestos, silica, or coal dust can cause pneumoconiosis, which may develop into serious lung disease. The size of the particle, ventilatory rate, and depth of breathing will determine the extent of pulmonary deposition. 

Berico, M A. Luciani, and M. Formignani, Atmospheric Aerosol in an Urban Area—Measurements of TSP and PM10 Standards and Pulmonary Deposition Assessments, Atmos. Environ., 31, 3659-3665 (1997). 

The pulmonary deposition of an aerosol depends on (Matthys and Kohler 1985)... 

Matthys, H. and Kohler, D. (1985). Pulmonary deposition of aerosols by different mechanical devices. Respiration, 48, 269-276. 

The systemic availability of inhaled budesonide has been measured in 15 healthy volunteers, using an open crossover design. Each subject was given three treatments, intravenous budesonide 0.5 mg, inhaled budesonide (from a metered-dose inhaler with a Nebuhaler) 1 mg (200 micrograms x 5) plus oral charcoal, and inhaled budesonide 1 mg without oral charcoal. The treatment order was randomized. The mean systemic availability of inhaled budesonide compared with intravenous budesonide was 36% with charcoal and 35% without charcoal, indicating that the absorption of budesonide from the gastrointestinal tract did not contribute to its systemic availability. Pulmonary deposition was 36% with charcoal and 34% without. When the inhaler was used incorrectly, that is, the canister was shaken only before the first of the five inhalations, systemic availability fell by 50%. This shows that the performance of each inhaler is very dependent on proper use (16). 

Pulmonary deposition efficiency Location of pulmonary deposition Pulmonary residence time (dissolution rate and other factors) Oral bioavailability Degree of oral deposition Systemic clearance Volume of distribution Protein binding... 

The delivery system plays a key role in determining the overall pulmonary deposition (percent of drug deposited in the lung), the amount of swallowed drug, and the regional deposition within the lung. All three factors are important for the degree of pulmonary selectivity. 

Pulmonary deposition efficiency depends on physicochemical characteristics, such as density of the aerosol or dry powder particles [33-35], Generally, particle diameters less than than 5 pm are required for efficient pulmonary delivery [36, 37], Pulmonary deposition also depends on the nature of the delivery device and differs between metered dose inhalers (MDIs). For example, pulmonary deposition expressed as the ratio of pulmonary versus total (pulmonary + oral) absorbed drug, ranged from 15-55% for a number of salbutamol devices and from 66-85% for drugs with lower oral bioavailabilities such as budesonide. 

Traditionally, pulmonary deposition of MDIs has been in the range of 10-20% [38-40], An increase in pulmonary deposition efficiency of MDIs has been achieved with the use of spacer devices [41-46], Aerosol deposition in the human lung has also been optimized after administration from a microprocessor-controlled pressurized MDI [47, 48], Improvement of pulmonary deposition of up to 40%... 

The pharmacokinetic/dynamic parameters involved in pulmonary dmg delivery of glucocorticoids have been reviewed. Among these, low oral bioavailability, high pulmonary deposition, pronounced clearance, and sustained pulmonary release are the most important parameters to be considered. 

S. Newman, K. Steed, G. Hooper, A. Kallen, and L. Borgstrom, Comparison of gamma scintigraphy and a pharmacokinetic technique for assessing pulmonary deposition of terbutaline sulphate delivered by pressurized metered dose inhaler, Pharm. Res. 72 231 (1995). 

Smith, R.M., L.D. Traber, D.L. Traber, and R.G. Spragg. 1989. Pulmonary deposition and clearance of aerosolized a-1-proteinase inhibitor administered to dogs and to sheep. J. Clin. Invest. 84 1145-1154. 

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