title: P-glycoprotein and drug therapy in organ transplantation.
abstract: The role of multidrug resistance and P-glycoprotein (P-gp) in the development of drug-resistant tumor cells has been extensively studied. As more knowledge on the physiological functions of P-gp has accumulated, the effects of P-gp modulation on the pharmacokinetics and the pharmacodynamics of many drugs have become apparent. Solid organ transplant recipients receive numerous medications that are substrates for P-gp. The objective of this review is to discuss the effects of P-gp modulation on the pharmacokinetics and the pharmacodynamics of immunosuppressive agents such as cyclosporine, tacrolimus, sirolimus, and corticosteroids. Pharmacokinetic alterations may occur in drug absorption since P-gp is in the small bowel, in drug distribution since P-gp functions in the blood-brain barrier, in drug metabolism since P-gp and cytochrome P450 3A have linked functions, and in drug elimination since P-gp is in the bile canaliculi and renal tubules. A link between P-gp and organ rejection has been speculated since upregulation of the P-gp pump may restrict immunosuppressant drug entry into immunocompetent cells. A further understanding of P-gp regulation upon chronic exposure to P-gp substrates and inhibitors and the potential administration of selective P-gp inhibitors will enhance our ability to use potent immunosuppressive drugs in organ transplant patients.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Lo
authors.forename: G J
authors.initials: GJ
authors.lastname: Burckart
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016377:Organ Transplantation
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents