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Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Sirolimus monotherapy in liver transplantation
F Di Benedetto1, S Di Sandro, N De Ruvo
1Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy. f.diben@virgilio.it
Introduction:
Since 1999, a new immunosuppressive drug was administered to renal transplant patients. The SRL molecule acts by blocking post-receptor signal transduction of interleukin-2 (IL-2) interacting with a family of intracellular binding proteins termed immunophilins FKBPs. Among these FKBPs, FK506 12-kd binding protein is the most relevant. SRL is an immunosuppressive drug. Therefore it can inhibit the immune system; at the same time the drug is not nephrotoxic, neurotoxic, and without diabetogenic effects.
Methods:
Among 285 patients who underwent liver transplantation, 27 took Sirolimus as monotherapy. Immunosuppressive treatment upto cyclosporine (CsA) or tacrolimus (FK) associated with steroids (methylprednisolone) and mycophenolate Mofetil (MMF) was initiated among subjects with pre-transplant renal failure. SRL was administered as monotherapy for patients who developed nephrotoxicity, or neurotoxicity, or diabetes. Moreover, patients affected by multifocal HCC who did not meet the Milan criteria or patients who developed Kaposi's Sarcoma were prescribed SRL monotherapy.
Results:
Nephrotoxicity occurred in 14 patients with mean serum creatinine level 2.2 mg/dl. Eleven patients with real failure showed significant improvements after a mean period of 28 days of SRL monotherapy (range: 6-45 days). The mean creatinine serum level after treatment with SRL monotherapy was 1.0 mg/dl (range: 0.7-1.2 mg/dl). Neurotoxicity occurred in 4 patients with tremor, confusion, and agitation. Each patient had complete improvement of symptoms after a few days of Sirolimus monotherapy. Among Three patients who developed Kaposi's Sarcoma, two underwent remission. One patient had diabetes due to calcineurin inhibitors, and one showed arterial hypertension not treatable with drugs. After the switch, we treated these patients with medications. Another important indication was HCC not meeting the Milan criteria.
Conclusion:
SRL monotherapy may be used to manage complication of calcineurin inhibitors or Kaposi's Sarcoma.
