Comparison of Cyclosporine Concentrations 2 Hours Post-Dose Determined Using 3 Different Methods and Trough Level in Pediatric Renal Transplantation

Abstract

Immunosuppression has been one of the great challenges in pediatric recipients of kidney allografts. Cyclosporine (CsA) has evolved during the past 25 years of transplantation. It requires frequent blood level monitoring because of its narrow therapeutic window and interpatient and intrapatient variability. Neoral (Novartis) is no exception. Ideally, monitoring of blood levels should also include determination of the area under the time-concentration curve (AUC) to better target the therapeutic window, thus avoiding underdosing or overdosing, especially in pediatric patients. A single blood concentration measurement 2 hours after Neoral administration (C2) has been shown to be a more for accurate predictor of drug exposure than trough levels (C0). Therefore, its use may lead to reduction in the incidence and severity of cellular rejection and of CsA toxicity. Some studies have shown that the metabolites/CsA ratio is substantially lower using C2 than C0, however, the between-assay differences for C2 monitoring have not been considered. The purpose of this study was to evaluate CsA C0 and C2 levels, determined using monoclonal fluorescence polarization immunoassay (FPIA)/TDx and enzyme multiplied immunoassay (EMIT). CsA levels were determined using a radioimmunoassay (RIA) in 30 pediatric transplant recipients with stable renal function within 42.7 mean months follow-up. Mean age was 13.4 years; 15 children were girls; 23 patients were recipients of cadaveric kidneys. The mean CsA microemulsion dose was 5.7 mg/kg/d. The 3 methods showed a high correlation between C0 and C2 ( r ≥ 0.97). A linear regression slope was significantly higher for C0 than C2 ( P < .001). The CsA concentrations both at C0 and C2 were significantly higher with FPIA than with RIA ( P < .009) but no differences were found for EMITT ( P = .2). The mean C0 level for FPIA was 22% and 26% higher than RIA and EMIT, respectively. The mean C2, for FPIA was 7% and 12% higher than RIA and EMIT, respectively. In conclusion, CsA levels determined using RIA or EMIT are better than using FPIA/Tx; also, C2 CsA levels are more accurate than C0 in pediatric transplantation patients.