ROUTINE USE OF ABBREVIATED AUC PHARMACOKINETIC MONITORING TO DOSE ADJUST CYCLOSPORINE EMULSION (NEORAL??) COMBINED WITH MYCOPHENOLATE MOFETIL IN ADULT RENAL TRANSPLANTATION

Abstract

320 Neoral® (Neo) has been demonstrated to be a superior form of oral cyclosporin (CSA) due to its increased bioavalability. Monitoring of blood levels using the abbreviated area under the curve (AAUC) has been tauded as a simple, convenient and more effective method than trough levels for adjustment of Neo dose (Kahan, et al., 1997). We report our prospective, non-randomized results in 70 non-consecutive, adult renal transplants in whom AAUC Neo dosing was applied in combination with mycophenolate mofetil (MMF) and prednisone (pred). Methods. Between July, 1997 and December, 1998, 46 cadaver (Cad) and 24 living donor (LD) renal transplants were analyzed. Neo was dosed at 5 mg/kg initially and adjusted to trough levels in the immediate postoperative period. Beginning the second week post-transplant and periodically thereafter, Neo levels were obtained at 2 & 6 hrs post dose to calculate AAUC. Neo dose was adjusted according to Table 1. MMF doses were begun at 1 g bid and reduced for those patients with adverse symptoms. Pred was tapered to 5 mg qd over a 6 month period. Patients excluded from this analysis had a history of complicated rejection of a previous renal transplant or the presence of another solid organ transplant. Results. See Table 2.Table 1Table 2: Recipient DemographicsOver-all rejection rates during the first 9 months were 11% for Cad and 8% for LD recipients. All LD recipients remain on protocol except 1 who developed early CSA-nephrotoxicity. Forty-one (89%) Cad recipients remain on protocol. Three of 4 Cad recipients with rejection were converted to tacrolimus. Two patients were taken off calcinurin-inhibitors due to HUS (1) and CSA-nephrotoxicity (1). Two patients were converted to azathioprine due to side-effects of MMF. At 1 yr, over-all mean Neo dose was 2.9±0.8 mg/kg/d and tended to be lower for LD recipients compared to Cad recipients (2.4 vs. 3.0). 80% of recipients remaining on protocol were taking Neo at 150mg or less bid at 1 year. Discussion. Our preliminary results demonstrate that AAUC monitoring of Neoral® can be used safely and effectively in combination with mycofenolate mofetil to achieve early, low dosing of maintenance CSA. Continued analysis of this patient population is necessary to delineate if this approach to maintenance immunosupression allows further reduction in Neo dosing. The potential long-term benefits of cost reduction and lower rates of chronic CSA-induced nephrotoxicity remain to be determined.