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Cyclosporine therapeutic window evaluation by Chebyshev's inequality method in kidney recipients
by
Aurelija Noreikaitė 1,*, Franck Saint-Marcoux 2,3, Edmundas Kaduševičius 1 and Edgaras Stankevičius 1
Aurelija Noreikaitė 1,*, Franck Saint-Marcoux 2,3, Edmundas Kaduševičius 1 and Edgaras Stankevičius 1
1
Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
2
Laboratory of Clinical Pharmacology, Faculty of Medicine, University of Limoges, Limoges, France
3
Department of Pharmacology and Toxicology, University Hospital, Limoges, France
*
Author to whom correspondence should be addressed.
Medicina 2014, 50(1), 37-43; https://doi.org/10.1016/j.medici.2014.05.008
Published: 6 June 2014
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.
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.
Keywords:
Cyclosporine; Therapeutic window; Cyclosporine concentration; Kidney transplantation; Pharmacokinetics
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Noreikaitė, A.; Saint-Marcoux, F.; Kaduševičius, E.; Stankevičius, E. Cyclosporine therapeutic window evaluation by Chebyshev's inequality method in kidney recipients. Medicina 2014, 50, 37-43.
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