Phase III elimination

Conjugation of lipophilic xenobiotics to polar cellular constituents renders the xenobiotic more water-soluble. While the lipophilic parent xenobiotics could readily diffuse into the cells, the increase in polarity associated with conjugation greatly reduces the ability of the compound to diffuse across the lipid bilayer of the cell membrane thus trapping the compound within the cell. The polar conjugates must therefore rely upon active transport processes to facilitate efflux from the cell. Hepatocytes, as well as other cells involved in chemical detoxification, are rich with members of the ATP-binding cassette superfamily of active transport proteins (ABC transporters). Cellular efflux of xenobiotics by these transporters is often referred to as Phase III elimination because Phase I or II detoxification processes often precede and are a requirement of Phase III elimination. A detailed description and discussion of elimination and transporters is presented in Chapter 15. 

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