title: The impact of drug transporters on adverse drug reaction.
abstract: In this review, we have highlighted the adverse drug reaction mediated by transporters from two aspects: (1) competitive interactions between drug and drug/metabolite/endogenous substance mediated by transporters; (2) the expression/function change of transporter due to physiologic factors, disease, and drugs induction. It indicated that transporters exhibited a broad substrate specificity with a degree of overlap, which could change the pharmacokinetics of drugs and cause toxicity due to competition interactions among substrates. In addition, the expression and function of transporters were regulated by physiological conditions, pathological conditions, and drugs induction, which could cause adverse drug reaction and interindividual differences. Furthermore, one substrate was always medicated by several transporters and often subjected to metabolism by CYP enzymes, so we should be more aware of the increased plasma concentration of drugs caused by drug transporters as well as drug metabolizing enzymes synergistically, especially for drugs with narrow therapeutic window. In addition, the weightiness for one transporter to induce drugs plasma/tissue concentration change could be different in different condition. On the whole, transporters were corresponding with systemic/organs exposure of drug/metabolites/endogenous compounds. So understanding the expression and function in drug transporters will result in better strategies for optimal dosage regimen and reduce the risk for drug adverse reaction as well as adverse drug-drug interactions.
authors: Department of Pharmacy, First Hospital of Lanzhou University, Lanzhou, 730000, China.
authors: Yan
authors: Y
authors: Zhou
authors: Guo-Qiang
authors: GQ
authors: Zhang
authors: Yu-Hui
authors: YH
authors: Wei
authors: Jian-Ping
authors: JP
authors: Zhang
authors: Guo-Rong
authors: GR
authors: Zhang
authors: Jiang-Xia
authors: JX
authors: Ren
authors: Hao-Gang
authors: HG
authors: Duan
authors: Zhi
authors: Z
authors: Rao
authors: Xin-An
authors: XA
authors: Wu
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004364:Pharmaceutical Preparations