Lung, drug metabolism

Cho, M., C. Chichester, C. Plopper, and A. Buckpitt. Biochemical factors important in Clara cell selective toxicity in the lung. Drug Metabol. Rev. 27 369-386, 1995. 

Hunt, C. A., Rustum, Y. M., Mayhew, E., and Papahadjopoulos, D. (1979). Retention of cytosine arabinoside in mouse lung following intravenous administration in liposomes of different size, Drug Metabol. Dispos., 7, 124-128. 

Ma J, Bhat M, Rojanasakul Y (1996) Drug metabolism and enzyme kinetics in the lung. In Hickey AJ (ed.) Inhalation Aerosols. Marcel Dekker Inc, New York. 

Most phase one reactions are catalyzed by the drug-metabolizing enzymes (mixed function oxidases, oxygenases) located in the endoplasmic reticulum of liver and, to a lesser extent, in intestine, kidney, and lung. These enzymes have been the subject of intensive research (G7, G8, LI). 

Drug metabolism can occur in all tissues and most biological fluids. However, the widest range of metabolic reactions occurs in the liver. A more substrate-selective range of metabolic processes takes place in the kidney, lungs, brain, placenta and other tissues. 

Wynalda MA, Hutzler JM, Koets MD et al. (2003) In vitro metabolism of clindamycin in human liver and intestinal microsomes. Drug Metab Dispos 31 878-887 Yost GS (1999) Sites of metabolism lung. In Wolf TF (ed) Handbook of Drug Metabolism. Marcel Dekker, New York pp 263-278... 

When feasible, the route of exposure in the test species should be the same as the clinical route of administration. An alternative route may be used if it gives similar metabolism and systemic exposure, particularly to relevant organs, such as the lung for inhalation agents, as the clinical route. Supportive drug metabolism and toxicokinetic data are generally required for selection of an alternative route of administration. 

Quantitatively, the smooth endoplasmic reticulum of the hepatocyte is the principal organelle of drug metabolism. Other sites of drug metabolism include epithelial cells of the gastrointestinal tract, the lungs, the kidneys and the skin. These sites are usually responsible for localised toxicity reactions. 

Arif JM, Khan SG, Aslam M, et al. 1992. Diminution in kerosene-mediated induction of drug metabolizing enz5mies by asbestos in rat lungs. Pharmacol Toxicol 71 37-40. 

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