PHARMACOKINETICS OF CYCLOSPORINE IN PEDIATRIC LONG-TERM LIVER-TRANSPLANT RECIPIENTS CONVERTED FROM SANDIMMUN TO NEORAL

Absorption of cyclosporin from the microemulsion formulation Neoral is less variable than from Sandimmun. Because of a lack of data in pedia tric liver transplant recipients, the pharmacokinetic profiles with Sa ndimmun and Neoral were compared in a conversion study. Thirty-eight c hildren with stable graft function were converted 2-12.3 years post-tr ansplant at a 1:1 ratio. The trough-level (C-min) with Neoral was 123 +/- 39 ng/ml versus 134 +/- 29 ng/ml with Sandimmun (P = NS), the area under the time-concentration curve (AUC) was 3325 +/- 1125 ngh/ml ve rsus 2423 +/- 846 ngh/ml (P < 0.001), the peak concentration (C-max) was 650 +/- 280 ng/ml versus 337 +/- 142 ng/ml (P < 0.001), and the me dian time to C-max was 2 h (range 0.5-3 h) versus 4 h (range 1-8 h; P < 0.05). The weak correlation between C-min and AUC with Sandimmun (r = 0.5; P = NS) was improved by using Neoral (r = 0.7; P < 0.001). The best predictor of AUC was the 2-h concentration (C-2h) of Neoral (r = 0.9; P < 0.001). Increased absorption and a more predictable pharmacok inetic profile with Neoral permit safer therapeutic monitoring in chil dren. The exclusive measurement of Neoral-C-2h allows one to estimate drug exposure with high precision (> 90%).