NOF-11

A one-year pediatric randomized double-blind comparison of neoral versus sandimmune in orthotopic liver transplantation

Fernando Alvarez, Paul R. Atkison, David R. Grant, Nathalie Guilbault, Adrian B. Jones, Peter S W Kim, Norman M. Kneteman, Liane Laurin, Steven R. Martin, Gerard F. Murphy, Khazal Paradis, James Shapiro, Lesley J Smith, Riccardo A. Superina

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background. Although cyclosporine (CsA) has been a mainstay in liver transplantation immunosuppression the original formulation [Sandimmune (SIM)] has variable absorption, particularly in children. Neoral is a new formulation of CsA that may have improved biovailability that would be advantageous in children. This study was undertaken to assess the pharmacokinetics (PK) and effects on outcome of Neoral versus Sandimmune (SIM) in primary pediatric liver transplant recipients. Methods. Thirty-two patients were randomized to receive Neoral (17 patients) or SIM (15 patients) in the early posttransplant period (days 1-7) in a double-blind fashion. Intravenous CsA was instituted immediately posttransplant followed by Neoral or SIM as soon as the patient was tolerating oral fluids (days 1-7). PK were compared after the first dose (1-7 days), 3 weeks, and 6 and 12 months posttransplant. In addition, side effects, effect of age and food on absorption, and rejection episodes were assessed by intent to treat analysis. Notable characteristics of this study include the use of a central laboratory for all sample analyses and the assessment of renal function using radioisotopic evaluation of glomerular filtration rates. Results. At baseline the two groups were comparable. Neoral resulted in higher peak levels of CsA and total drug exposure with comparable time to peak drug levels at days 1-7 and week 3. This trend was maintained at 6 and 12 months. Time on i.v. CsA was reduced in the Neoral group (8.4 vs. 11.1 days) and the weight adjusted daily dose of SIM required to achieve target trough levels was about 2-fold more than Neoral from day 22 onward. In addition, biopsy proven and treated and steroid-resistant rejection episodes were fewer in the Neoral group (6 vs. 12; P=0.01 and 1 vs. 8: P=0.004, respectively). Side effects were comparable in both treatment groups. Conclusions. Neoral was well tolerated and had greater biovailability than SIM without any increase in the incidence of side effects. In addition fewer episodes of rejection were observed with Neoral versus SIM. We conclude that Neoral is the CsA formulation of choice for use in pediatric liver transplant recipients.

Original languageEnglish
Pages (from-to)87-92
Number of pages6
JournalTransplantation
Volume69
Issue number1
StatePublished - Jan 15 2000
Externally publishedYes

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Liver Transplantation
Cyclosporine
Pediatrics
Pharmacokinetics
Liver
Glomerular Filtration Rate
Pharmaceutical Preparations
Immunosuppression

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Alvarez, F., Atkison, P. R., Grant, D. R., Guilbault, N., Jones, A. B., Kim, P. S. W., ... Superina, R. A. (2000). NOF-11: A one-year pediatric randomized double-blind comparison of neoral versus sandimmune in orthotopic liver transplantation. Transplantation, 69(1), 87-92.

NOF-11 : A one-year pediatric randomized double-blind comparison of neoral versus sandimmune in orthotopic liver transplantation. / Alvarez, Fernando; Atkison, Paul R.; Grant, David R.; Guilbault, Nathalie; Jones, Adrian B.; Kim, Peter S W; Kneteman, Norman M.; Laurin, Liane; Martin, Steven R.; Murphy, Gerard F.; Paradis, Khazal; Shapiro, James; Smith, Lesley J; Superina, Riccardo A.

In: Transplantation, Vol. 69, No. 1, 15.01.2000, p. 87-92.

Research output: Contribution to journalArticle

Alvarez, F, Atkison, PR, Grant, DR, Guilbault, N, Jones, AB, Kim, PSW, Kneteman, NM, Laurin, L, Martin, SR, Murphy, GF, Paradis, K, Shapiro, J, Smith, LJ & Superina, RA 2000, 'NOF-11: A one-year pediatric randomized double-blind comparison of neoral versus sandimmune in orthotopic liver transplantation', Transplantation, vol. 69, no. 1, pp. 87-92.
Alvarez F, Atkison PR, Grant DR, Guilbault N, Jones AB, Kim PSW et al. NOF-11: A one-year pediatric randomized double-blind comparison of neoral versus sandimmune in orthotopic liver transplantation. Transplantation. 2000 Jan 15;69(1):87-92.
Alvarez, Fernando ; Atkison, Paul R. ; Grant, David R. ; Guilbault, Nathalie ; Jones, Adrian B. ; Kim, Peter S W ; Kneteman, Norman M. ; Laurin, Liane ; Martin, Steven R. ; Murphy, Gerard F. ; Paradis, Khazal ; Shapiro, James ; Smith, Lesley J ; Superina, Riccardo A. / NOF-11 : A one-year pediatric randomized double-blind comparison of neoral versus sandimmune in orthotopic liver transplantation. In: Transplantation. 2000 ; Vol. 69, No. 1. pp. 87-92.
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abstract = "Background. Although cyclosporine (CsA) has been a mainstay in liver transplantation immunosuppression the original formulation [Sandimmune (SIM)] has variable absorption, particularly in children. Neoral is a new formulation of CsA that may have improved biovailability that would be advantageous in children. This study was undertaken to assess the pharmacokinetics (PK) and effects on outcome of Neoral versus Sandimmune (SIM) in primary pediatric liver transplant recipients. Methods. Thirty-two patients were randomized to receive Neoral (17 patients) or SIM (15 patients) in the early posttransplant period (days 1-7) in a double-blind fashion. Intravenous CsA was instituted immediately posttransplant followed by Neoral or SIM as soon as the patient was tolerating oral fluids (days 1-7). PK were compared after the first dose (1-7 days), 3 weeks, and 6 and 12 months posttransplant. In addition, side effects, effect of age and food on absorption, and rejection episodes were assessed by intent to treat analysis. Notable characteristics of this study include the use of a central laboratory for all sample analyses and the assessment of renal function using radioisotopic evaluation of glomerular filtration rates. Results. At baseline the two groups were comparable. Neoral resulted in higher peak levels of CsA and total drug exposure with comparable time to peak drug levels at days 1-7 and week 3. This trend was maintained at 6 and 12 months. Time on i.v. CsA was reduced in the Neoral group (8.4 vs. 11.1 days) and the weight adjusted daily dose of SIM required to achieve target trough levels was about 2-fold more than Neoral from day 22 onward. In addition, biopsy proven and treated and steroid-resistant rejection episodes were fewer in the Neoral group (6 vs. 12; P=0.01 and 1 vs. 8: P=0.004, respectively). Side effects were comparable in both treatment groups. Conclusions. Neoral was well tolerated and had greater biovailability than SIM without any increase in the incidence of side effects. In addition fewer episodes of rejection were observed with Neoral versus SIM. We conclude that Neoral is the CsA formulation of choice for use in pediatric liver transplant recipients.",
author = "Fernando Alvarez and Atkison, {Paul R.} and Grant, {David R.} and Nathalie Guilbault and Jones, {Adrian B.} and Kim, {Peter S W} and Kneteman, {Norman M.} and Liane Laurin and Martin, {Steven R.} and Murphy, {Gerard F.} and Khazal Paradis and James Shapiro and Smith, {Lesley J} and Superina, {Riccardo A.}",
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AU - Atkison, Paul R.

AU - Grant, David R.

AU - Guilbault, Nathalie

AU - Jones, Adrian B.

AU - Kim, Peter S W

AU - Kneteman, Norman M.

AU - Laurin, Liane

AU - Martin, Steven R.

AU - Murphy, Gerard F.

AU - Paradis, Khazal

AU - Shapiro, James

AU - Smith, Lesley J

AU - Superina, Riccardo A.

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N2 - Background. Although cyclosporine (CsA) has been a mainstay in liver transplantation immunosuppression the original formulation [Sandimmune (SIM)] has variable absorption, particularly in children. Neoral is a new formulation of CsA that may have improved biovailability that would be advantageous in children. This study was undertaken to assess the pharmacokinetics (PK) and effects on outcome of Neoral versus Sandimmune (SIM) in primary pediatric liver transplant recipients. Methods. Thirty-two patients were randomized to receive Neoral (17 patients) or SIM (15 patients) in the early posttransplant period (days 1-7) in a double-blind fashion. Intravenous CsA was instituted immediately posttransplant followed by Neoral or SIM as soon as the patient was tolerating oral fluids (days 1-7). PK were compared after the first dose (1-7 days), 3 weeks, and 6 and 12 months posttransplant. In addition, side effects, effect of age and food on absorption, and rejection episodes were assessed by intent to treat analysis. Notable characteristics of this study include the use of a central laboratory for all sample analyses and the assessment of renal function using radioisotopic evaluation of glomerular filtration rates. Results. At baseline the two groups were comparable. Neoral resulted in higher peak levels of CsA and total drug exposure with comparable time to peak drug levels at days 1-7 and week 3. This trend was maintained at 6 and 12 months. Time on i.v. CsA was reduced in the Neoral group (8.4 vs. 11.1 days) and the weight adjusted daily dose of SIM required to achieve target trough levels was about 2-fold more than Neoral from day 22 onward. In addition, biopsy proven and treated and steroid-resistant rejection episodes were fewer in the Neoral group (6 vs. 12; P=0.01 and 1 vs. 8: P=0.004, respectively). Side effects were comparable in both treatment groups. Conclusions. Neoral was well tolerated and had greater biovailability than SIM without any increase in the incidence of side effects. In addition fewer episodes of rejection were observed with Neoral versus SIM. We conclude that Neoral is the CsA formulation of choice for use in pediatric liver transplant recipients.

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