Therapeutic durg monitoring of cyclosporin using area under the curve in nephrotic syndrome

Abstract

The use of cyclosporin in nephrotic syndrome can be considered in cortico-resistance or cortico-dependence. Cyclosporin is an immunosuppressant with a narrow therapeutic range and large pharmacokinetics variability justifying its therapeutic drug monitoring (TDM). The aim of this study was to evaluate the TDM of cyclosporin by the measurement of AUC0-12h in patients with nephrotic syndrome and to study the correlations between the AUC0-12h and the different blood concentrations of cyclosporin. It is a retrospective study from 2009 to 2016. TDM of cyclosporin was carrying out by ARCHITECT®. Determination of the AUC0-12h was made from three samples taken at T0, T60min and T180min obtained by a model of population pharmacokinetics of cyclosporin. A total of 20 patients were evaluated (29 abbreviated kinetics). The median AUC0-12h was 4.76 mg*h/L. Considering the target 5 mg*h/L during the first 6 months, 6 AUC0-12h were sub-therapeutic and 5 supra-therapeutic, no AUC0-12h was in the therapeutic range. Considering the 3 mg*h/L as a target during the following months, 13 AUC0-12h among 18 were supra-therapeutic. A correlation coefficient between the AUC0-12h of cyclosporin and C0 was 0.798. Correlation between AUC0-12h and C2h was 0.909. The median C2h found in our work was 878 ng / mL during the first six months versus 1039 ng / mL in the following months. Our patients are overexposed to cyclosporin and TDM of this drug by determination of AUC0-12h or by C2h would be more interesting than TDM by C0. TDM allows a better individual dose adjustment to avoid especially toxicity of cyclosporin.