In pharmaceutical therapy, the onset of pharmacological and adverse effects of drugs varies widely among individuals. Since these effects are mostly dependent on the blood level of each drug, it is particularly important to monitor and regulate those levels after drug administration. Factors influencing the pharmacokinetics and pharmacodynamics of drugs include drug transporters, drug metabolizing enzymes and the plasma protein-binding ratio. Among these factors, we focused on P-glycoprotein (P-gp), a drug efflux transporter. The expression and function of P-gp are reported to alter under several pathological conditions and by administrating some foods or substrate drugs for P-gp. In this mini-review, we introduce alterations in the expression and functional activity of P-gp by anti-cancer drugs, most of which are P-gp substrates, in addition to their mechanism of action. In tumorous or healthy tissues, the expression and function of P-gp were increased by chronic exposure to anti-cancer drugs. A large number of previous studies have proposed that not only various transcriptional factors for P-gp but also post-translational factors such as ezrin/radixin/moesin are involved in changes in P-gp. The expression and function of P-gp seem to be altered during anti-cancer treatment possibly through the above pathways, which may in turn affect the pharmacokinetics and pharmacodynamics of drugs. Therefore, the response should take into account the kinds of drugs each patient uses and their status of P-gp expression and function in clinical pharmacotherapy.

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.