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 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 (Cmin) 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 (Cmax) was 650 +/- 280 ng/ml versus 337 +/- 142 ng/ ml (P < 0.001), and the median time to Cmax was 2 h (range 0.5-3 h) versus 4 h (range 1-8 h; P < 0.05). The weak correlation between Cmin 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 (C2h) 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-C2h allows one to estimate drug exposure with high precision (> 90%).
Melter
M
M
Kinderklinik, Medizinischen Hochschule Hannover, Germany.
Rodeck
B
B
Kardorff
R
R
Hoyer
P F
PF
Brodehl
J
J
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004304:Dosage Forms; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007408:Intestinal Absorption; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D013997:Time Factors
D004304:Dosage Forms; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine