Altered functions and expressions of drug transporters in liver, kidney and intestine in disorders of local and remote organs: possible role of oxidative stress in the pathogenesis.
BACKGROUND
Oxidative stress is important in the pathogenesis of various diseases. Drug transporters expressed in the liver, kidney and intestine regulate the distribution, elimination and absorption of drugs. These procedures of drugs in diseases of these organs, mediated by drug transporters, often fluctuate and thereby cause inter- and intra-individual pharmacokinetic variability.


OBJECTIVE
In the present review article, we explore recent reports demonstrating the variance of expressions and/or functions of drug transporters in diseases of the liver, kidney and intestine, in which oxidative stress is involved at least in part in their etiology, and summarize perspectives for further study and the application to clinical situations.


CONCLUSIONS
Various ATP binding cassette and solute carrier transporter expressions were up- or down-regulated in remote organs as well as in the local organ of diseases when these organs were injured, at least in part by oxidative stress, suggesting that oxidative stress is a factor affecting the expression and function of drug transporters. The present review provides useful information for further investigation on the roles of drug transporters in inter- and intra-individual pharmacokinetic variability and for refining dosing regimens in the state of organ diseases.
Ikemura
Kenji
K
Mie University Graduate School of Medicine, Department of Clinical Pharmacy and Biopharmaceutics, Tsu, Mie 514-8507, Japan.
Iwamoto
Takuya
T
Okuda
Masahiro
M
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007410:Intestinal Diseases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*
D002352:Carrier Proteins