Cyclosporine therapeutic window evaluation by Chebyshev's inequality method in kidney recipients

Objective: The aim of this study was to identify a cyclosporine therapeutic range for kidney recipients.
Materials and methods: The cyclosporine exposure level was based on the calculation of the mean area under the concentration-time curve AUC_(0–12). The AUC_(0–12) was estimated using a Bayesian estimator and a 3-point limited sampling strategy. Cyclosporine exposure levels were obtained from 3 blood samples: 0, 1, and 3 h postdose; and analyses were performed using a liquid chromatography–tandem mass spectrometry method. The therapeutic window of cyclosporine was calculated by the Chebyshev's inequality method with a 99% guarantee (a = 0.01) using the IBM SPSS Statistics 20 software.
Results: It was found that the therapeutic window of cyclosporine estimated by the Cheby- shev's inequality method and put on the AUC_(0–12) exposure lies in the ranges from 2.84– 3.13 mg h/L with the 99% confidence for the patients with the target AUC_(0–12) exposure of 3.8 mg h/L (posttransplantation time >1 year). The therapeutic window of cyclosporine differs in different posttransplantation time groups: the estimated AUC exposure range in the group of patients who have a graft longer than 5 years is 2.70–2.98 mg h/L, and the estimated AUC exposure range in the group of patients who have a graft for 1–5 years is 3.05–3.75 mg h/L.
Conclusions: Chebyshev's inequality could be an appropriate and more precise method to determine the therapeutic window for cyclosporine in kidney recipients than the target AUC_(0–12) value and further studies should be conducted to evaluate patients with postoperative time <1 year.