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Comparison of pharmacokinetics of neoral and sandimmune in stable pediatric liver transplant recipients
Author(s) -
van Mourik Indra D. M.,
Thomson Mike,
Kelly Deirdre A.
Publication year - 1999
Publication title -
liver transplantation and surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1074-3022
DOI - 10.1002/lt.500050203
Subject(s) - cmax , pharmacokinetics , medicine , trough level , liver transplantation , transplantation , area under the curve , ciclosporin , urology , gastroenterology , pharmacology , tacrolimus
Cyclosporine (Sandimmune; Novartis Pharmaceuticals UK Ltd) is an effective immunosuppressive drug, but its lipid formulation and variable absorption may expose children to the risk of rejection during episodes of gastroenteritis after liver transplantation. Neoral (Novartis) is a microemulsified form of cyclosporine that may be better absorbed. In this study, the pharmacokinetic profiles of Neoral and Sandimmune were compared in stable children after liver transplantation to evaluate whether Neoral is more predictably absorbed. Eight children, 6 boys and 2 girls, with a mean age of 4.5 years (range, 1.2‐12) were studied between 4 and 12 months after liver transplantation. Pharmacokinetic profiles were performed on each child by using the same dose (mg/kg) of Neoral or Sandimmune. T max , C max , C trough , and the area under the curve (AUC) were calculated and side effects were documented in children taking either drug for more than 3 months. Mean peak cyclosporine levels were higher and were achieved significantly sooner with Neoral (C max 790.5 ± 216.5 ng/mL, P = .06; T max 1.8 ± 1.0 hr, P = .01) than with Sandimmune (C max 589.4 ± 313 ng/mL, T max 2.5 ± 1.7 hr), implying more rapid and better absorption. There was no significant difference in overall drug exposure (AUC) and 12‐hour trough levels between the two formulations ( P > .05). Children with Roux‐en‐Y loop biliary anastomosis taking Neoral, however, showed greater increases in AUC (mean increase = 37%) than those with duct‐to‐duct anastomosis (mean increase = 16%). There was no correlation between 12‐hour trough level and AUC for either Neoral ( r 2 = 0.48) or Sandimmune ( r 2 = −0.08); however, for both drugs, AUC correlated very well with the 2‐hour post‐dose level ( r 2 = 0.68 and 0.7, respectively). Hirsutism was reported in 4 of 6 children on Neoral and may be associated with higher peak levels. Neoral is more consistently absorbed than Sandimmune in children after liver transplantation and may be more effective prophylaxis against rejection. Because of the increased peak levels and drug exposure, which may influence side effects, particularly in children with Sandimmune malabsorption, we recommend a 1:0.75 dose conversion ratio in patients being converted from Sandimmune to Neoral.