A Systems Biology View of Drug Transporters

SNPs were identified in the Japanese population for the organic cation transporter 1 (OCTI), and when functionally characterized in vitro, the uptake of cations was reduced significantly for some of these mutations, indicating that this would likely contribute to interindividual variations in metabolism of drugs that are transported via OCTI [13]. The sodium-dependent carnitine cotransporter OCTN2 can also possess mutations that result in primary carnitine deficiency, thus impacting fatty acid oxidation that is characterized by many clinical manifestations [14]. 

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While such lipophilidty similarity matrices do not consider the 3D structures of the molecules, they seem to be appropriate for the incorporation of nonlinear lipophilicity-activity relationships in 3D QSAR analyses, e.g. in CoMFA studies. At least from a theoretical point of view lipophiUcity similarity matrices should be preferred when the nonlinear lipophilicity-activity relationship does not result from binding but from transport and distribution of the drugs in the biological system, which most often is the case. 

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