Functional Alterations of Intestinal P-Glycoprotein under Diabetic Conditions

概要

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The maintenance of an appropriate serum concentration of a drug is known to be important for its pharmacological effects and the prevention of unexpected adverse effects. Functional alterations of drug transporters and drug-metabolizing enzymes may influence the serum concentration of drugs through changes in its pharmacokinetics and pharmacodynamics (PK/PD). There are many drug transporters expressed in the brain, liver, kidneys, and intestine including ATP-binding cassette (ABC) transporters and solute carriers (SLCs), which contribute to the systemic distribution of various drugs. Furthermore, the expression and function of P-glycoprotein (P-gp), one of the ABC transporters, is altered by environmental factors such as lifestyle and disease. In this review, we have focused on the influence of functional alterations in the intestinal P-gp on the PK/PD of drugs administered via the oral route under diabetic conditions. Altered expression patterns of intestinal P-gp observed under diabetic conditions exhibit pathological stage-dependency. Furthermore, many factors, such as serum glucose, insulin, nitric oxide, and cytokines, influence expression of intestinal P-gp. Finally, to design appropriate and individually targeted pharmacotherapy, it is necessary to consider the influence of alterations in the intestinal P-gp as well as drug metabolizing enzymes under diabetic conditions based on experimental results obtained from fundamental animal research.