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Mycophenolic acid pharmacokinetics in stable pediatric renal transplantation

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Abstract

Mycophenolate mofetil (MMF) is given to children in fixed doses based either on body weight or body surface area. There are data indicating mycophenolic acid (MPA) blood levels should be monitored in the early period of transplantation. However, there is little information regarding MPA pharmacokinetics (PK) in stable pediatric recipients. We evaluated MPA-PK in 20 stable renal transplant children (11.7±1.9 years) under long-term (46±31 months) MMF (26.1±7 mg/kg per day or 785±183 mg/m2 per day) therapy plus prednisone and cyclosporin A (n=16), tacrolimus (n=3), or MMF/prednisone (n=1). Total MPA levels were measured using the EMIT-MPA assay at 0, 1, 2, 3, 4, 6, and 8 h after an oral dose of MMF. The level at 12 h was considered equal to the trough level for AUC0–12 calculation. Mean C0, Cmax, AUC 0–12, and Tmax were 3.46±1.32, 13.5±0.58 μg/ml, 63.2±24.4 μg.h/ml, and 1.3±0.6 h, respectively. Six (30%) children were considered to have an adequate exposure (36–54 μg.h/ml) to MPA, 11 (55%) showed an AUC0–12 >54 μg.h/ml, and 3 (15%) showed an AUC0–12 <36 μg.h/ml. A Cmax ≥10 μg/ml was seen in 13 (65%) children. MMF dose did not correlate with AUC0–12 or Cmax. The combination of variables C0, C1, and C4 provided an equation to predict exposure (r 2=0.75) where AUC0–12=12.62+(7.78xC0)+(0.90xC1)+(1.30xC2) (P<0.001). The use of MMF without monitoring MPA blood levels may cause unnecessary overexposure to the drug in stable pediatric recipients.

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Acknowledgements

This study was partially supported by Dade-Behring-Brazil and presented at the ATC 2002, Annual Meeting of the AST/ASTS, Washington, and at the World Congress of Transplantation, Miami 2002, USA.

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Authors and Affiliations

  1. Renal Transplant Unit, Division of Urology and Nephrology, Hospital das Clínicas da Faculdade de Medicina, University of São Paulo, São Paulo, Brazil

    Elias David-Neto, Lilian Monteiro Pereira Araujo, Maria Cristina Ribeiro Castro, Cristiane Feres Alves, Erica Kakehashi, Elisa Midori Yagyu, Margaret Queiroga, William Carlos Nahas & Luiz Estevam Ianhez

  2. Central Laboratory, Hospital das Clínicas da Faculdade de Medicina, University of São Paulo, São Paulo, Brazil

    Nairo Massakazu Sumita, Maria Elizabeth Mendes & Paschoalina Romano

  3. , Rua Ferdinando Laboriau 263, 01250–040 São Paulo, Brazil

    Elias David-Neto

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  1. Elias David-Neto
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  2. Lilian Monteiro Pereira Araujo
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  3. Nairo Massakazu Sumita
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Correspondence to Elias David-Neto.

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David-Neto, E., Araujo, L.M.P., Sumita, N.M. et al. Mycophenolic acid pharmacokinetics in stable pediatric renal transplantation. Pediatr Nephrol 18, 266–272 (2003). https://doi.org/10.1007/s00467-002-1057-1

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  • DOI: https://doi.org/10.1007/s00467-002-1057-1

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