Premium
Adequate Early Cyclosporin Exposure is Critical to Prevent Renal Allograft Rejection: Patients Monitored by Absorption Profiling
Author(s) -
Clase C. M.,
Mahalati K.,
Kiberd B. A.,
Lawen J. G.,
West K. A.,
Fraser A. D.,
Belitsky P.
Publication year - 2002
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2002.20814.x
Subject(s) - medicine , profiling (computer programming) , urology , renal transplant , kidney , computer science , operating system
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 (AUC 0−4 ) and cyclosporin (CyA) levels immediately before and at 2 and 3 h after dosing (C 0, C 2 and C 3 ) 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 AUC 0−4 . Of the single time‐point measurements, the measurement properties of C 2 were closest to those of AUC 0−4 , and superior to those of C 3 . The relationship between C 0 and subsequent AR was weak and did not reach statistical significance. On day 3, CyA AUC 0−4 ≥ 4400 ng . h/mL and C 2 ≥ 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.