Simultaneous estimation of cyclosporin and mycophenolic acid areas under the curve in stable renal transplant patients using a limited sampling strategy

Objectives: Area under the curve (AUC)-based monitoring of cyclosporin (CsA) could help to optimise therapeutic drug monitoring in certain transplant patients in addition to trough concentration monitoring. It is the method of choice for mycophenolic acid (MPA). The objective of this study was to develop a limited sampling strategy for simultaneous estimation of CsA and MPA AUCs in long-term renal transplant patients. Methods: Twenty kidney transplant patients treated with CsA and mycophenolate mofetil were included in a pharmacokinetic study more than 6 months after transplantation. Multilinear regression analyses were performed to develop a model enabling the estimation of both drugs' AUCs using a limited number of samples. Dose-normalised data were used throughout the analysis. Results: Trough concentrations of MPA were poorly correlated with AUC, either used alone (r2=0.232) or together with other concentrations. Several models for CsA AUC estimation met the predefined criteria (r2>0.9, P<0.05). The AUC of MPA was best estimated by a three-concentration model (AUC=0.58 C20 min+0.97 C1 h+6.64 C3 h+3.48; r2=0.946). These sampling times also applied to CsA AUC (AUC=1.17 C20 min+0.68 C1 h+5.36 C3 h+4.24; r2=0.985). AUCs estimated using these models in our patients using the jack-knife procedure were found to be precise and unbiased as compared with reference trapezoidal AUCs. Conclusion: We were able to develop a multilinear regression model for simultaneous estimation of both CsA and MPA AUCs using only three blood samples taken up to 3 h post-dosing.