title: Functional alterations of intestinal P-glycoprotein under diabetic conditions.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University.
authors.forename: Takuro
authors.initials: T
authors.lastname: Kobori
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamoto
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokuyama
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019440:Anti-Obesity Agents; D007004:Hypoglycemic Agents