title: Role of efflux pumps and metabolising enzymes in drug delivery.
abstract: The impact of efflux pumps and metabolic enzymes on the therapeutic activity of various drugs has been well established. The presence of efflux pumps on various tissues and tumours has been shown to regulate the intracellular concentration needed to achieve therapeutic activity. The notable members of efflux proteins include P-glycoprotein, multi-drug resistance protein and breast cancer resistance protein. These efflux pumps play a pivotal role not only in extruding xenobiotics but also in maintaining the body's homeostasis by their ubiquitous presence and ability to coordinate among themselves. In this review, the role of efflux pumps in drug delivery and the importance of their tissue distribution is discussed in detail. To improve pharmacokinetic parameters of substrates, various strategies that modulate the activity of efflux proteins are also described. Drug metabolising enzymes mainly include the cytochrome P450 family of enzymes. Extensive drug metabolism due to the this family of enzymes is the leading cause of therapeutic inactivity. Therefore, the role of metabolising enzymes in drug delivery and disposition is extensively discussed in this review. The synergistic relationship between metabolising enzymes and efflux proteins is also described in detail. In summary, this review emphasises the urgent need to make changes in drug discovery and drug delivery as efflux pumps and metabolising enzymes play an important role in drug delivery and disposition.
authors.affiliation: University of Missouri-Kansas City, Division of Pharmaceutical Sciences, School of Pharmacy, 64110-2499, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Katragadda
authors.forename: Balasubrahmanyam
authors.initials: B
authors.lastname: Budda
authors.forename: Banmeet S
authors.initials: BS
authors.lastname: Anand
authors.forename: Ashim K
authors.initials: AK
authors.lastname: Mitra
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D018432:Drug Resistance, Multiple; D015316:Genetic Therapy; D006801:Humans; D049329:Nanostructures; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics; D011355:Prodrugs / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D004364:Pharmaceutical Preparations; D011355:Prodrugs; D003577:Cytochrome P-450 Enzyme System