title: Cyclosporine therapeutic window evaluation by Chebyshev's inequality method in kidney recipients.
abstract: OBJECTIVE
  The aim of this study was to identify a cyclosporine therapeutic range for kidney recipients.
  
  
  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 3h 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 (α=0.01) using the IBM SPSS Statistics 20 software.
  
  
  RESULTS
  It was found that the therapeutic window of cyclosporine estimated by the Chebyshev'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.
authors: Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania. Electronic address: aurelija.noreikaite@lsmuni.lt.
authors: Aurelija
authors: A
authors: Noreikaitė
authors: Laboratory of Clinical Pharmacology, Faculty of Medicine, University of Limoges, Limoges, France; Department of Pharmacology and Toxicology, University Hospital, Limoges, France.
authors: Franck
authors: F
authors: Saint-Marcoux
authors: Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Edmundas
authors: E
authors: Kaduševičius
authors: Institute of Physiology and Pharmacology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
authors: Edgaras
authors: E
authors: Stankevičius
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001499:Bayes Theorem; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: Cyclosporine; Cyclosporine concentration; Kidney transplantation; Pharmacokinetics; Therapeutic window