Respiratory tract clearance mechanisms

Schlesinger RB. The interaction of inhaled toxicants with respiratory tract clearance mechanisms. Crit Rev Toxicol 1990 20 257-285. 

Palmer 1989 Robinson et al.1983). However, the ratio was almost certainly affected by initial chelation with Ca-DPTA, followed by daily intravenous therapy with the chelating agent, Zn-DPTA, treatments that would have increased the urinary excretion of americium (Breitenstein and Palmer 1989). The above not withstanding, the observations made on this subject demonstrate that fecal excretion was an important pathway of excretion in this subject long after mechanical clearance of americium from the respiratory tract would have been complete. This is consistent with observations made in nonhuman primates that show that americium is excreted into bile (see Section 3.4.4.4). However, the extent to which the biliary excretion pathway in humans might resemble that of nonhuman primates is not known. 

From a drug delivery perspective, the components of the host defence system comprise barriers that must be overcome to ensure efficient drug deposition as well as retention in and absorption from the respiratory tract. Important non-absorptive clearance mechanisms include mucociliary clearance, alveolar macrophages and metabolism (Figure 6.2). 

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. 

Aerosols must be respirable, that is, have a mean aerodynamic diameter of less than 5 xm, to ensure that a reasonable proportion will penetrate the respiratory tract defence systems of the nasal passages and the mucociliary clearance mechanisms. 

Particle dimension is crucial for the distribution of particles in the various regions of the human respiratory tract. The various mechanisms of clearance act differently for nano and micro-sized particles.1... 

ABSORPTION AND OTHER CLEARANCE MECHANISMS IN THE RESPIRATORY TRACT... 

Absorption of the protein and peptide molecules delivered to the respiratory tract competes against various other clearance mechanisms. When a particle containing a therapeutic substance is deposited in the... 

Information on the distribution of strontium absorbed after deposition in the respiratory tract can be derived from studies in which strontium compounds were instilled directly into the trachea. Although intratracheal instillation does not mimic inhalation exposure, the distribution of the absorbed strontium is likely to be similar to that which would be absorbed after inhalation. In rats that received an intratracheal dose of 89Sr-enriched fly ash (sieved to have a particle diameter of distribution of 90% less than 20 pm), radioactivity was eliminated from the lung and appeared in plasma and other tissues within days of the exposure tissue plasma concentration ratios were >1 (1.5-2) in the liver, kidney, stomach, and small intestine, and <1 (0.7-0.9) in the spleen, heart, and brain (Srivastava et al. 1984b). The relatively high concentrations of strontium in the gastrointestinal tract may reflect the mechanical clearance of strontium from the airways to the esophagus. 

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