Drug-metabolizing Enzymes and Transporters

Pharmacogenomics of Drug-Metabolizing Enzymes and Drug Transporters in Chemotherapy... 

The extent of oral absorption of a drug depends on physical properties of the drug (e.g., solubility and membrane permeability) and its interaction with various enzymatic processes of an organism. The two most prominent enzymatic systems are drug metabolic enzymes and drug transporters. Both metabolic enzymes and transporters exist as many related forms that generally have distinct, yet potentially overlapping, substrate specificities. 

Urquhart, B. L., Tirona, R. G., and Kim, R. B. (2007) Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters implications for interindividual variability in response to drugs. J. Clin. Pharmacol. 47, 566-578. 

By definition, the intrinsic clearance (CLjnt) is calculated by dividing the elimination velocity of a drug (v) by the drug concentration at the target site (Jusko, 1992). The activity of metabolizing enzymes and drug transporters can also be determined as the intrinsic clearance by in vitro experiments. As discussed later, we can extrapolate CLjnt values determined in vitro to in vivo CLjnt values. 

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