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The compelling case for therapeutic drug monitoring of mycophenolate mofetil therapy

Pediatric Nephrology volume 32, pages 21–29 (2017)Cite this article

Abstract

We have reviewed current evidence on the therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in relationship to drug efficacy and safety. The relationship between actual MPA exposure and mycophenolate mofetil (MMF) dose has been shown to be weak in children and adolescents. The TDM of MPA exposure should ideally be performed using full pharmacokinetic profiles or limited sampling strategies. Recent evidence has provided some rationale for using the post-dose trough level as a single measure. In terms of short-term efficacy, there is strong evidence that a MPA area under the time–concentration curve of >30 mg × h/L reduces acute rejection episodes early after renal transplantation, and there is evolving evidence that aiming for the same exposure over the long term may be a viable strategy to reduce the formation of donor-specific antibodies. Strong evidence also supports the existence of important drug interactions and age/developmental dependent differences in drug metabolism that may necessitate the need for TDM of MMF therapy. Based on these findings and given the substantial inter- and intra-patient variability of MPA exposure, it would appear that MMF therapy should be subject to TDM to avoid over- and under-dosing. This may be a viable strategy to reduce treatment-emergent adverse events and to increase the effective pediatric transplant survival rates.

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Acknowledgments

Ana Catalina Alvarez-Elías is a CONACYT fellow and received support from Programa de Maestria y Doctorado en Ciencias Médicas, Facultad de Medicina UNAM.

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Authors and Affiliations

  1. Department of Pediatrics, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5 W9, Canada

    Guido Filler & Ana Catalina Alvarez-Elías

  2. Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N5A 5A5, Canada

    Guido Filler

  3. Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5 W9, Canada

    Guido Filler & Christopher McIntyre

  4. Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico

    Ana Catalina Alvarez-Elías

  5. Laboratorio de Investigacion en Nefrologia, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico

    Ana Catalina Alvarez-Elías & Mara Medeiros

  6. Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, Mexico

    Mara Medeiros

  7. Department of Pediatrics, Children’s Hospital, London Health Science Centre, Western University, 800 Commissioners Road East, London, ON, N6A 5 W9, Canada

    Guido Filler

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  1. Guido Filler
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Filler, G., Alvarez-Elías, A.C., McIntyre, C. et al. The compelling case for therapeutic drug monitoring of mycophenolate mofetil therapy. Pediatr Nephrol 32, 21–29 (2017). https://doi.org/10.1007/s00467-016-3352-2

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  • DOI: https://doi.org/10.1007/s00467-016-3352-2

Keywords

  • Mycophenolate mofetil
  • Mycophenolic acid
  • Therapeutic drug monitoring
  • Trough level
  • Ontogeny
  • Intra-patient variability