Adequate Early Cyclosporin Exposure is Critical to Prevent Renal Allograft Rejection: Patients Monitored by Absorption Profiling

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Abstract

This study used receiver operating characteristic analysis to investigate the properties of area under the concentration-time curve during the first 4 h after cyclosporin-microemulsion dosing (AUC0−4) and cyclosporin (CyA) levels immediately before and at 2 and 3 h after dosing (C0, C2 and C3) to predict the risk of biopsy-proven acute rejection (AR) at 6 months. Ninety-eight kidney transplant recipients treated with CyA-microemulsion-based triple therapy immunosuppression were studied on post-transplant days 3, 5, and 7, and at increasing intervals thereafter.

The most sensitive and specific predictor of AR was AUC0−4. Of the single time-point measurements, the measurement properties of C2 were closest to those of AUC0−4, and superior to those of C3. The relationship between C0 and subsequent AR was weak and did not reach statistical significance. On day 3, CyA AUC0−4≥ 4400 ng . h/mL and C2≥ 1700 ng/mL were each associated with a 92% negative predictive value for rejection in the first 6 months. Pharmacokinetic measurements on or after day 5, and measurements on day 3 in patients with delayed graft function, were not predictive of AR.

Adequate exposure within the first 3 days post transplantation may be critically important in preventing subsequent rejection.

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