Aerosols respiratory absorption

Industrial environments expose individuals to a plethora of airborne chemical compounds in the form of vapors, aerosols, or biphasic mixtures of both. These atmospheric contaminants primarily interface with two body surfaces the respiratory tract and the skin. Between these two routes of systemic exposure to airborne chemicals (inhalation and transdermal absorption) the respiratory tract has the larger surface area and a much greater percentage of this surface exposed to the ambient environment. Or dinary work clothing generally restricts skin exposures to the arms, neck, and head, and special protective clothing ensembles further limit or totally eliminate skin exposures, but breathing exposes much of the airway to contaminants. 

Clearance to pulmonary lymph nodes will occur at a fractional rate of 0.0001 per day. Dissolution of the deposited particles and absorption of cerium into the systemic circulation will occur at rates that are between the extremes represented by CeCh in CsCl particles and Ce oxide or Ce in fused aluminosilicate particles as given by the functions included in Figure 9. These rates should not be expected to be constant over the entire clearance period and will depend upon the overall composition of the bulk aerosol particles, which indude particle size, amount of stable lanthanide present, acidity, and the solubility of other components of the particles. The accuracy of predicting respiratory tract clearance and internal organ uptake of radiocerium will depend heavily upon adequate determination of the particle solubility characteristics. 

Pulmonary dynamics, the dimension and geometry of the respiratory tract and the structure of the lungs, together with the solubility and chemical reactivity of the inhalants greatly influence the magnitude of penetration, retention, and absorption of inhaled gases, vapors (Dahl, 1990), and aerosols (Raabe, 1982 Phalen, 1984). The quantity of an inhalant effectively retained in the pulmonary system constitutes the inhaled dose that causes pharmacotoxic responses. 

Human exposure to endrin may occur by ingestion, inhalation, or by dermal contact. Dermal absorption can be significant. Gastrointestinal absorption is enhanced by dietary fats. While not highly volatile, endrin-laden aerosols or dust particles can be trapped in respiratory mucus and swallowed, leading to gastrointestinal absorption. 

Ehrhardt C, Fiegel J, Fuchs S, Abu-Dahab R, Schaefer UF, Hanes J, Lehr CM (2002) Drug absorption by the respiratory mucosa Cell culture models and particulate drug carriers. J Aerosol Med 15 131-139... 

Substances that can be inhaled include gases, vapors, liquid aerosols (both liquid and solid substances in solution), and finely divided powders/dusts (dust aerosols). Such substances may be absorbed from the respiratory tract or, through the action of clearance mechanisms, may be transported out of the respiratory tract and swallowed. This means that absorption from the gastrointestinal tract will contribute to the total body burden of substances that are inhaled. 

Ribavirin can be administered as an aerosol using a small-particle aerosol generator. When administered by this route, the drug has only minimal systemic absorption, with drug concentrations in respiratory tract secretions approximately 100 times as high as those found in plasma. Oral absorption is rapid, and first-pass metabolism is extensive ribavirin s oral bioavailability is 64% and can be increased by administration with a high-fat meal. Steady-state levels are reached after 4 weeks. 

In addition to oral administration for hepatitis C infection in combination with interferon alfa, aerosolized ribavirin is administered by nebulizer (20 mg/mL for 12-18 hours per day) to children and infants with severe respiratory syncytial virus (RSV) bronchiolitis or pneumonia to reduce the severity and duration of illness. Aerosolized ribavirin has also been used to treat influenza A and infections but has not gained widespread use. Systemic absorption is low (< 1%). Aerosolized ribavirin is generally well tolerated but may cause conjunctival or bronchial irritation. Health care workers should be protected against extended inhalation exposure. The aerosolized drug may precipitate on contact lenses. 

In addition, size reduction can also enhance delivery of poorly water-soluble APIs to the respiratory tract. SpeciLcally, aerosolized particles should have aerodynamic diameters in the range of 1-5(xm. With larger particles, deposition occurs primarily on the back of the throat, which can lead to systemic absorption and undesired side effects. 

Data on the absorption, distribution, metabolism, and excretion of hydrogen chloride are sparse. There are reports of severe nonlactic metabolic acidosis developing rapidly after ingestion of hydrochloric acid (suggesting systemic absorption from the gastrointestinal tract), but this effect has not been reported after dermal exposure to concentrated hydrochloric acid or after inhalation of hydrogen chloride vapor or aerosol. No studies were found on upper respiratory... 

Depending on the physicochemical natme of the toxic gas or aerosol, absorption will take place at different areas of the respiratory tract. Apart from the chemical properties the size of particles and aerosols will also affect the targeted area. Materials with diameters less than 2 pm will reach the alveoli whereas larger ones (about 20 pm in diameter) are retained in the upper respiratory areas of throat and bronchi thus protecting gas exchange in the lung. 

Hirst, P.H. Bacon, R.E. Newman, S.P. Armer, T. Mohsen, N. Pavkov, R. Byron, D. Deposition, absorption and bioavailability of aerosolized morphine sulfate delivered by a novel hand-held device, the metered solution inhaler (MSI). In Respiratory Drug Delivery VII Dalby, R.N., Byron, P.R., Parr, S.J., Peart, J., Eds. Interpharm Press, 2000 467 69. 

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