Pharmacokinetics of cyclosporine in pediatric long-term liver transplant recipients converted from Sandimmun to Neoral

Abstract

Absorption of cyclosporin from the microemulsion formulation Neoral is less variable than from Sandimmun. Because of a lack of data in pediatric liver transplant recipients, the pharmacokinetic profiles with Sandimmun and Neoral were compared in a conversion study. Thirty-eight children with stable graft function were converted 2–12.3 years post-transplant 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 ng_*h/ml versus 2423 ± 846 ng_*h/ml (P < 0.001), the peak concentration (C_max) was 650 ± 280 ng/ml versus 337 ± 142 ng/ml (P < 0.001), and the median 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_{2 h}) of Neoral (r = 0.9; P < 0.001). Increased absorption and a more predictable pharmacokinetic profile with Neoral permit safer therapeutic monitoring in children. The exclusive measurement of Neoral-C_{2 h} allows one to estimate drug exposure with high precision ( > 90 %).