Genetic Polymorphism in drug transport

Many different drug transporters are expressed in various tissues, such as

the epithelial cells of the intestine and kidney, hepatocytes, and brain
capillary endothelial cells. Some of these are responsible for drug transport
in various tissues, and they may be key determinants of the pharmacokinetic
characteristics of a drug as far as its intestinal absorption, tissue distribution,
and elimination are concerned. Transporters have been classified as primary,
secondary, or tertiary active transporters.

Transporter pharmacogentics is rapidly developing field that is concerned with drug uptake and efflux
into or through tissues. Significant problems in clinical applications result from poor or variable oral drug
bio-availability and high intra- and interindividual variation in pharmacokinetics.

Drug efflux is the important cause of drug resistance in certain type of cells. In cytotoxic chemotherapy
for several human cancerous diseases, drugs are generally very effective, but in cases of intrinsic or
acquired multidrug resistance, usually highly effective anti-neoplastic compounds,eg, vincristine,
Vinblastine, daunorubicin, or doxorubicin, fail to produce cures. One of the major causes of such
multidrug resistance is the appearance of special integral membrane proteins the P-glycoprotein
multidrug transporter, or MDRI, which is one of the major causes of low drug level in targeted cells.
The multidrug resistance-associated proteins (MRPs) are members of the ATP-binding cassette (ABC)
superfamily with six members currently, of which MRP1, MRP2, and MRP3 are commonly known to
affect drug disposition. MRP1 is distributed all over the body. Substrates for MRP1 include glutathione,
glucuronide, and sulfate. MRP1 is expressed basolaterally