Biomonitoring of cyclosporine in renal transplant patients

Cyclosporine is a potent immunosuppressive drug. It has a very complex pharmacokinetics and has many influential factors. Which requiring therapeutic drug monitoring (TDM) to ensure a better compromise between efficacy and toxicity. Measurement of the area under the blood concentration-time curve (AUC 0-12h ) is reflective of total drug exposure. However, the measurement of AUC 0-12h implies many problems. Thus, it is more clinically acceptable to use a single blood sample as a surrogate index of total drug exposure. Our patients are routinely monitored by simultaneous determination of C 0 and C 2 and occasionally by determination of AUC 0-12h . The present investigation aimed to evaluate the effectiveness of our strategy of biomonitoring of cyclosporine and to improve the interpretation of the results based mainly on the comparison of our TDM results with different therapeutic ranges proposed in the literature, and the results of the usual TDM parameters (C 0 /C 2 ) with the reference index (AUC 0-12h ). This study was carried out in two steps: The first step was a retrospective descriptive study, spread over a period of 7 years, of a population of 32 kidney transplant recipients treated with an immunosuppressive regimen combining cyclosporine, steroids, and mycophenolate mofetil (MMF). For the entire population, the AUC 0-12h was calculated using the limited sampling equation established by Einecke et al, 2002. The second step is an analytical cross-sectional study of a subpopulation of 10 kidney transplant recipients. In this subgroup, an estimation was carried out from C 0 , C 1 , and C 3 by the Bayesian estimator developed by the INSERM team of Limoges. The present investigation demonstrated that the AUC 0-12h calculated in our population is not significantly different from that observed in the reference population monitored by AUC 0-12h , given that our clinicians relied mainly on C 0 for cyclosporine biomonitoring in this population, this allowed us to judge biomonitoring by C 0 as potentially effective. This mean AUC 0-12 coincides with the C 2 distribution used to propose the new C 2 margins, suggesting that they are more appropriate for our population.The biomonitoring of cyclosporine in kidney recipients can be performed by a single C 0 assay. Alternatively, the calculation of AUC 0-12h by limited sampling formula or the Bayesian method could be used occasionally. The C 2 assay seems impractical in clinical routine unless used with other concentrations for AUC 0-12h estimation.