Lungs absorption from

Lung Absorption from Yes Metabolism via airways vs. Dose formulation Other Pulmonary transit times... 

The major routes of uptake of xenobiotics by animals and plants are discussed in Chapter 4, Section 4.1. With animals, there is an important distinction between terrestrial species, on the one hand, and aquatic invertebrates and fish on the other. The latter readily absorb many xenobiotics directly from ambient water or sediment across permeable respiratory surfaces (e.g., gills). Some amphibia (e.g., frogs) readily absorb such compounds across permeable skin. By contrast, many aquatic vertebrates, such as whales and seabirds, absorb little by this route. In lung-breathing organisms, direct absorption from water across exposed respiratory membranes is not an important route of uptake. 

Schanker, L. S., Mitchell, E. W., Brown, R. A., Jr., Species comparison of drug absorption from the lung after aerosol inhalation or intratrachael injection, Drug Metab. Dispos. 1986,... 

Harley, N.H., and P.S. Pasternack, Experimental Absorption Applied to Lung Dose from Radon Daughters, Health Phys.,23, 771-782, (1972). 

Hexachloroethane has been found in the plasma of workers wearing protective clothing and respiratory protection suggesting that hexachloroethane can be absorbed following inhalation and/or dermal exposure. Based on the minimal effects seen on target tissues (liver and kidney) in animal studies, absorption from the lungs seems to be limited. Dermal absorption was also estimated to be low based on calculated dermal penetration rates. 

Absorption, Distribution, Metabolism, and Excretion. There are no mechanistic or quantitative studies of hexachloroethane absorption from the lungs or across the gastrointestinal tract or skin. However, absorption does occur following oral exposure based on the appearances of hexachloroethane and its metabolites in blood, urine, and exhaled air (Fowler 1969b Gorzinski et al. 1985 Jondorf et al. 1957 Mitoma... 

The absorption of inhaled -hexane has been investigated in six healthy male volunteers (Veulemans et al. 1982). Three different trials were performed on each volunteer 4-hour exposure at 102 ppm -hexane 4-hour exposure at 204 ppm, and exposure during exercise on a stationary bicycle ergometer at 102 ppm. Each trial was done at least two weeks apart. Lung clearance (from alveolar air to blood) and retention were calculated from -hexane concentrations in inhaled and expired air. After exposure, /7-hcxane in exhaled air was measured for up to 4 hours to determine respiratory elimination. Retention of -hexane (calculated from lung clearance and respiratory minute volume) was approximately 20-25%... 

Manford F, Tronde A, Jeppson A-B, Patel N, Johansson F, Forbes B (2005) Drug permeability in 16HBE14o- airway cell layers correlates with absorption from the isolated perfused rat lung. Eur J Pharm Sci 26 414—420. 

Niven RW, Byron PR (1988) Solute absorption from the airways of the isolated rat lung. I. The use of absorption data to quantify drug dissolution or release in the respiratory tract. Pharm Res 5 574—579. 

Figure 10.2 Apparent permeability coefficients (Papp) observed in vitro across Calu-3 ( ) [62] and 16HBE14o- (o) [72] cell layers vs. in vivo rate constants (Ka) determined for absorption from the rat lung after intratracheal delivery of various molecules.

Schanker LS (1978) Drug absorption from the lung. Biochem Pharmacol 27(4) 381-385... 

Absorption occurs through the respiratory tract, orai membranes, and skin (Taylor 1996). Absorption from the stomach is iimited, uniess the acidity is reduced, because nicotine is a strong base. Between 80 and 90% of nicotine is metabolized, mainly in the liver but also the kidneys and lungs. Cotinine is the primary metabolite of nicotine, and the half-life of nicotine is about 2 hours. Elimination occurs by the kidneys, but it is also present in the breast milk of lactating women. 

Absorption, Distribution, Metabolism, and Excretion. Human data indicate that chloroform absorption from the lungs is rapid and fairly complete (Smith et al. 1973). The data also indicate that absorption after oral exposure is fairly complete for both animals and humans (Brown et al. 1974a Fry et al. 1972 Taylor et al. 1974). Although there are no experimental data regarding dermal absorption in humans, some data have been extrapolated from mouse studies (Tsumta 1975). The rate of absorption following oral or inhalation exposure is rapid (within 1-2 hours). Additional animal studies investigating the rate of dermal absorption would be useful to quantitate dermal absorption and to compare information from oral and inhalation studies. 

Proteases occurring in the epithelial lining fluids are another source of variability in protein absorption from the lung. In the epithelial lining fluids proteases and peptidases do occur. Inhibition of proteases and peptidases with substances such as bacitracin or aprotinin might improve the bioavailability of proteins. For example bacitracin was shown to increase insulin bioavailability by a factor of 6.8 [3]. 

Wolfe et al. 1970 Wolfsdorf and Kundig 1972). However, limited absorption from the gastrointestinal tract into the lungs may also occur (Mann et al. 1977). 

Kerosene is a mixture of aliphatic and aromatic hydrocarbons, naphthenes (cycloalkanes) and other organic compounds. Systemic absorption from the lungs or stomach can cause central nervous system depression. The oil has a low surface tension and low viscosity so that small quantities can spread over a large surface area. This can affect the lungs, and... 

Following inhalation exposure, about 20-35% of nickel deposited in the lungs of humans is absorbed into the bloodstream. Absorption from the respiratory tract is dependent on the solubility of the nickel compound, with higher urinary nickel observed in workers exposed to soluble nickel compounds (nickel chloride, nicke sulfate) than in those exposed to less-soluble nickel compounds (nickel oxide, nickel subsulfrde). Following oral exposure, about 27% of the nickel given to humans in drinking water was... 

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