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Transplantation. 2000 Feb 15;69(3):432-6.

Stimulated response of peripheral lymphocytes may distinguish cyclosporine effect in renal transplant recipients receiving a cyclosporine+rapamycin regimen.

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University of Pittsburgh Medical Center, PA 15213, USA.



Clinically, cyclosporine (CSA, Neoral) is titrated to concentrations, and not to pharmacological effect.


Intracellular interleukin- (IL) 2 was measured in phorbol myristic acid-ionomycin-stimulated peripheral lymphocytes by flow cytometry, after isolation from 14 renal transplant recipients receiving CSA+prednisone, and double-blind rapamycin (rapamycin:placebo=4:1).


The proportion (%) of CD4+IL-2+ lymphocytes corresponding to CSA levels (mean+/-SD ng/ml) measured preoperatively (TO=O), and on postoperative day 8, before (356+/-63), and 2 hr after the morning dose (Cmax=1567+/-669), decreased from 39+/-16 to 15+/-8 and 3+/-1.6, respectively. Reciprocally, unresponsive lymphocytes (%CD4+IL-2-) increased with increasing CSA levels and predicted an EC50 of 249 ng/ml (CSA concentration at which CD4+IL-2- cells increased by 50% over baseline) in an Emax pharmacodynamic model.


Clinically, the pharmacological effect of CSA is quantifiable, and lies in the upper end of the predicted range. In our Neoral-treated sample population, Cmax was associated with the least variable "cyclosporine effect." Such information could potentially individualize immunosuppression, and lead to rational dosing strategies.

[Indexed for MEDLINE]

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