An important consideration, although somewhat underrated, for the predictive design of drugs is their lipophilicity, i.e. the relative hydrophilic and lipophilic properties of the molecules. On various occasions, this property has been interpreted as a measure of the permeation of drugs across cell membranes and their subsequent migration into the nucleus. The transport of anticancer drugs through alterations affected membranes in the lipophilicity of drugs and the prevailing media in passive transports, and the properties of the carrier systems used in active transports [1].
Partition or distribution coefficients are critical elements in efforts designed to describe the uptake, distribution, biotransformation, and excretion of organic chemicals in biological systems [2]. High log P values imply high solubility and good penetration of lipid membranes, but by implication, low solubility in aqueous phases, and, hence the inability for the molecule to be transported through the body. Molecules with high log P also tend to be substrates of the metabolizing cytochrome P450 enzymes in the liver, in which case, first pass effects can remove much of the administered drug candidate before it can reach its target area [3].
References:
1. Gnewuch C T and Sosnovsky G; Critical appraisals of approaches for predictive designs in anticancer drugs, Cell. Mol. Life Sci; 2002,59; 959 -1023.
2. Jepson G W, Black R K, Mccafferty J D, Mahle D A and Gearhart J M; A partition coefficient determination method for nonvolatile chemicals in biological tissues, Toxilogical Sciences; 1993, 22,4,519-524.
3. Nienke de Vries A, Beijnen J H, Boogerd W and Tellingen O V; Blood-brain barrier and chemotherapeutic treatment of brain tumors Future Drugs; 2006, 6,8, 1199-1209.
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