Comparison of peak and trough level monitoring of cyclosporine treatment using two modern cyclosporine preparations☆

Abstract 

Aims

Determination of the peak cyclosporine blood level instead of the trough level promises to represent an improvement in cyclosporine therapy monitoring due to better correlation with the AUC. In kidney transplant recipients we investigated whether this conclusion applies also to a new dispersion formulation of cyclosporine (Cicloral).

Patients

42 stable kidney transplant recipients were converted from Sandimmun Neoral (NEO) to Cicloral (CIC) in a 1:1 dose relation.

Methods

On the last day of NEO administration and 14 days after conversion to CIC a full 12 h cyclosporine AUC was performed using blood samples obtained prior to and at serial times after dosing. The correlations between cyclosporine levels at these time points and the AUC were determined for NEO and CIC. For each measurement, a predicted AUC was calculated by regression analysis. The prediction error for each sampling time was calculated separately for NEO and CIC.

Results

The cyclosporine trough levels showed the poorest correlation with AUC for both preparations (NEO: r = 0.187 vs CIC: r = 0.554). The best correlation was observed for samples obtained at three hours after intake of either CIC (r = 0.807) or NEO (r = 0.611). The number of 2 hours measurements that lead to an unacceptable estimate from the real AUC was somewhat lower for CIC (8/40 vs 11/41 with NEO).

Conclusions

Two- or three-hour cyclosporine level monitoring with the newer cyclosporine preparation Cicloral has at least the same precision as that of the original Neoral®. In this study, the newer preparation even showed a tendency towards superior monitoring properties.