Comparison of trough, 2-hour, and limited AUC blood sampling for monitoring cyclosporin (Neoral®) at day 7 post-renal transplantation and incidence of rejection in the first month

The use of alternative strategies to the traditional pre-dose/trough (C₀) blood sampling for cyclosporine (CsA) therapeutic drug monitoring has the potential to revolutionize analytical practices which have, in many centers, been established for some 20 years. While the C₀ sample has previously been recommended, current attitudes are increasingly proposing alternatives for assessing CsA exposure, including various limited sampling strategies of the AUC (_lssAUC) in the early postdose period, or alternative single-point nontrough samples, such as a 2-hour postdose sample (C₂). The present study has reviewed a series of consecutive renal transplant recipients over 18 months where CsA was the primary immunosuppressant. The _lssAUC performed at around day 7 posttransplantation included drawing blood at 0, 2, and 4 hours postdose, giving AUC_(0-4). The aim of this study was to review the occurrence of acute biopsy-proven rejection in the first month and consider which of (simultaneously measured) C₀, C₂ or AUC_(0-4) was a better early indicator of this adverse outcome. The result was best described by comparing the data from rejectors (n = 13) and nonrejectors (n= 42) for these 3 indices of CsA exposure (i.e., C₀, C₂ or AUC_(0-4). There was no evidence that C_O predicted the likelihood of such adverse clinical outcomes. In contrast, rejectors tended to have lower mean C₂ CsA concentrations, and the incidence of rejection was 0.0 when C2 exceeded 1200 μg/L (n = 10). While the data are limited in the higher C₂ CsA concentration range, it is nevertheless consistent with more recent recommendations suggesting that the CsA at C₂ should target 1700 μg/L in this first month posttransplantation. As 64% of the patients were also receiving a CsA-sparing agent (diltiazem [DTZ]), the relationships were also investigated to determine whether any affect of concomitant DTZ therapy could be demonstrated. However, in this small sample, no significant affect of DTZ was seen.