Razi Journal of Medical Sciences

  Background & Aim: Cyclosporine-A (CsA) is an immunosuppressant with a narrow therapeutic window. Inter-and-intrapatient variability in cyclosporine pharmacokinetics necessitates frequent blood level monitoring in transplant patients and total blood cyclosporine concentration used to allow dosage adjustment in transplant patients. The purpose of the present study was, first of all, to develop a precise and suitable method for therapeutic drug monitoring (TDM) of cyclosporine in children with renal transplant and to evaluate CsA blood concentrations in patients in order to find out the best time for sampling Iranian children with kidney transplant for TDM of cyclosporine. This can also help us achieve the best immunosuppressant with the least side effects for renal transplant patients.

  Patients and Method: In this experimental study, 29 pediatric transplant recipients (16 boys and 13 girls) who had received renal transplant at least six months prior to the study participated. The mean age of the patients was 14. 5 ±2. 3 years (ranging from 8 to 20 years),and they all showed stable renal function. The patients were also receiving other drugs such as prednisolone, mycophenolate mofetil, iron and folic acid. The clinical status of the patients was recorded. The CsA blood levels were determined using radioimmunoassay (RIA) 0, 0. 5, 1, 1. 5 and 2 hours after drug administration. The data analysis was performed using Pearson correlation coefficient.

  Results: Our results are indicative of good precision and�reproducibility of the method. Minimum detection limit of cyclosporine-A was 5 ng/ml and percentage yield was 86-109%. Inter-and-intraday variability for three cyclosporine-A blood concentrations were 8% and 5. 8% respectively. The mean blood concentrations 0. 5 and 1 hour after drug administration were 100 ± 3. 0 and 515± 19. 2 μ g/dl respectively. The mean serum creatinine level was 0. 9 (0. 1-1. 9) mg/dl. There was a high correlation between CsA dose, serum creatinin and C_{1. 5}, while there was no correlation between age, serum creatinine and C_{1. 5} level. Also, there was no correlation between C₀ and any of the above-mentioned parameters. These results show that C_{1. 5} level is the best indicator for TDM of cyclosporine-A in Iranian children and has the best correlation with dose and creatinin level.

  Conclusion: The developed method is precise,sensitive and suitable for therapeutic drug monitoring of cyclosporine-A. Using single point monitoring can help to improve the cooperation of patients during TDM procedure, and for this purpose C_{1. 5} level seems more accurate than C₀ level in pediatric transplant patients.