title: Effect of calcineurin inhibitor therapy on P-gp expression and function in lymphocytes of renal transplant patients: a preliminary evaluation.
abstract: Cyclosporine and tacrolimus are substrates and potent inhibitors of the multidrug transporter, P-glycoprotein, in vitro. The authors have investigated the effect of chronic therapy with these and other immunosuppressive drugs on the expression and function of P-glycoprotein in T lymphocytes. Using a P-gp antibody, the authors studied the level of expression of P-gp in CD4 and CD8 T cells over a period of time in renal transplant patients. For comparison, a group of healthy volunteers and patients who did not receive any calcineurin inhibitors but were maintained on mycophenolate mofetil was included. The P-gp expression on lymphocytes from these two groups remained constant (over several months' time). However, patients who were started on tacrolimus or cyclosporine had an initial decline in expression of P-gp on CD4 T cells. Patients who were initiated on calcineurin therapy on day 1 posttransplant also had a decrease in expression of P-gp on CD4 T lymphocytes. This preliminary analysis suggests that the calcineurin inhibitors might be modulating the expression and function of transporters in lymphocytes, thus changing not only the drug concentration but also the apparent efficacy of these drugs. Further understanding and elucidation of such effects would be important in understanding the relationship between pharmacokinetics and pharmacodynamics of these and other drugs, especially for immunosuppressive and anti-AIDS therapy.
authors.affiliation: Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco 94143-0446, USA.
authors.forename: Dolly A
authors.initials: DA
authors.lastname: Parasrampuria
authors.forename: Marianne V
authors.initials: MV
authors.lastname: Lantz
authors.forename: Jytte L
authors.initials: JL
authors.lastname: Birnbaum
authors.forename: Flavio G
authors.initials: FG
authors.lastname: Vincenti
authors.forename: Leslie Z
authors.initials: LZ
authors.lastname: Benet
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000502:physiology; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D016572:Cyclosporine; D016559:Tacrolimus