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Effect of Calcineurin Inhibitor Therapy on P‐gp Expression and Function in Lymphocytes of Renal Transplant Patients: A Preliminary Evaluation
Author(s) -
Parasrampuria Dolly A.,
Lantz Marianne V.,
Birnbaum Jytte L.,
Vincenti Flavio G.,
Benet Leslie Z.
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700222011337
Subject(s) - calcineurin , tacrolimus , medicine , pharmacodynamics , pharmacology , p glycoprotein , pharmacokinetics , transporter , cd8 , immunosuppressive drug , mycophenolate , renal function , mycophenolic acid , transplantation , immunology , immune system , biology , multiple drug resistance , drug resistance , biochemistry , gene , microbiology and biotechnology
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.