Monitoring of cyclosporin and azathioprine in organ transplantation.
Cyclosporin A (CsA) is a cyclic undecapeptide that was first isolated from the fungus Tricoderma polysporum. The introduction of this potent immunosuppressive compound significantly improved the outcome of solid organ and bone marrow allograft transplantation. There is now a large body of accumulated experience in the monitoring of this drug, and several consensus conferences have addressed this issue /1-3/. Azathioprine in CsA-based triple therapy with steroids is still widely used in organ transplantation even though it is known to carry the risk of severe myelosuppression. Measurement of white blood cell (WBC) and platelet counts is generally used to recognize azathioprine toxicity. However, recent reports /4-6/ have indicated that patients with a genetically determined deficiency in thiopurine methyltransferase (TPMT), an important enzyme in azathioprine metabolism, are at high risk for myelosuppression. Monitoring of active azathioprine metabolites, which are responsible both for the immunosuppressive action and for the toxicity of azathioprine, may be necessary in such cases. It should also be noted that the incidence of posttransplant lymphoproliferative disorder (PTLD) is a function of the intensity of immunosuppression /7,8/. Thus the combination of CsA, azathioprine and steroids is associated with an approximately three-fold higher incidence of PTLD than low dose CsA guided by therapeutic drug monitoring /8/.
Oellerich
M
M
Abteilung Klinische Chemie, Georg-August-Universität, Göttingen, Germany.
Schütz
E
E
Armstrong
V W
VW
D001379:Azathioprine / Q000378:metabolism; D016572:Cyclosporine / Q000378:metabolism; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D006801:Humans; D007118:Immunoassay; D007166:Immunosuppressive Agents / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D016377:Organ Transplantation
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine