The maintenance of an appropriate serum concentration of drug is important for effective pharmacological effect and prevention of unexpected adverse effects of drugs. The functional alterations of drug transporters and drugmetabolizing enzymes may influence the serum concentration of drugs and highly affect the pharmacokinetics and pharmacodynamics. There are many kinds of drug transporters in the liver, kidneys and intestines including ATPbinding cassette (ABC) transporters and solute carriers (SLCs) and they contribute to the disposition of various drugs. We focused on the influence of functional alterations of ＂intestinal＂ P-glycoprotein (P-gp), one of the ATP-dependent drug efflux pumps, on the pharmacokinetics and pharmacodynamics as the first barrier of orally-administered drugs.In this mini review, we introduce the influences of pathological conditions mainly focusing on diabetes on the P-gp protein expression levels and its drug-transport function in intestine. This mini review shows that the alteration pattern of intestinal P-gp expression levels under type 1 and type 2 diabetic conditions or intestinal ischemia has pathological stage-dependency and intestinal site specificity. Furthermore, there are many factors known to affect the intestinal P-gp expression levels such as serum glucose or insulin, nitric oxide or reactive oxygen species, and cytokines produced under diabetic condition. These variations observed in the diabetes are also confirmed in transient ischemic condition.In this mini review, we outline the alterations of intestinal P-gp expression including its possible mechanism and influences on the pharmacokinetics and pharmacodynamics under different pathological stages. In the clinical field, it is important to focus on the individual functional alterations of intestinal P-gp for effective and appropriate pharmacological therapeutics.

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