title: Adequate early cyclosporin exposure is critical to prevent renal allograft rejection: patients monitored by absorption profiling.
abstract: This study used receiver operating characteristic analysis to investigate the properties of area under the concentration-time curve during the first 4h after cyclosporin-microemulsion dosing (AUC0-4) and cyclosporin (CyA) levels immediately before and at 2 and 3h 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 > or = 4,400 ng.h/mL and C2 > or = 1,700 ng/mL were each associated with a 92% negative predictive value for rejection in the first 6months. 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 3days post transplantation may be critically important in preventing subsequent rejection.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Clase
authors.forename: K
authors.initials: K
authors.lastname: Mahalati
authors.forename: B A
authors.initials: BA
authors.lastname: Kiberd
authors.forename: J G
authors.initials: JG
authors.lastname: Lawen
authors.forename: K A
authors.initials: KA
authors.lastname: West
authors.forename: A D
authors.initials: AD
authors.lastname: Fraser
authors.forename: P
authors.initials: P
authors.lastname: Belitsky
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D012372:ROC Curve; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine