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Tacrolimus nephrotoxicity: beware of the association of diarrhea, drug interaction and pharmacogenetics

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Abstract

Tacrolimus is known to potentially lead to adverse events in recipients with diarrhoea and/or calcium channel blocker (CCB) co-administration. We report a renal transplant recipient who suffered from severe nephrotoxicity related to a toxic tacrolimus trough concentration in both conditions, diarrhoea and CCB co-administration, and with genotyped CYP3A system and P-glycoprotein (P-gp) polymorphisms. To our knowledge, this is the first case to be investigated for such polymorphisms. Clinicians should be reminded of the possibility of highly increased levels of tacrolimus in situations of diarrhoea and/or co-administration of CCBs. It also highlights the key role in tacrolimus pharmacokinetics of the CYP3A system and P-gp polymorphisms, and their influence in high-risk situations when enzyme activity is already affected by enterocyte damage due to diarrhoea and CCB competition.

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Fig. 1

Abbreviations

CCB:

Calcium channel blocker

CYP:

Cytochrome P450

MDR1:

Multi-drug resistance 1

P-gp:

P-glycoprotein

SNP:

Single nucleotide polymorphism

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Authors and Affiliations

  1. Department of Pediatric Nephrology, Armand-Trousseau Hospital, AP-HP and University Paris VI, 26 Avenue du Docteur Arnold Netter, 75012, Paris, France

    Sandrine Leroy, Arnaud Isapof, Albert Bensman & Tim Ulinski

  2. Department of Biology, University College London, London, UK

    Sonia Fargue

  3. Department of Pediatric Nephrology—Reference Centre for Rare Renal Diseases, Femme Mère Enfant Hospital, University of Lyon, Lyon, France

    Sonia Fargue

  4. Department of Pediatric Pharmacology—Pharmacogenetics and Clinical Investigation Center—CIC9202, Robert-Debré Hospital, AP-HP, Paris, France

    May Fakhoury & Evelyne Jacqz-Aigrain

  5. Department of Pediatric Nephrology, Robert-Debré Hospital, AP-HP, Paris, France

    Georges Deschênes

  6. Inserm UMR S938, Université Pierre et Marie Curie, Paris, France

    Tim Ulinski

Authors
  1. Sandrine Leroy
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  2. Arnaud Isapof
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  3. Sonia Fargue
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  4. May Fakhoury
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  7. Evelyne Jacqz-Aigrain
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  8. Tim Ulinski
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Correspondence to Tim Ulinski.

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Leroy, S., Isapof, A., Fargue, S. et al. Tacrolimus nephrotoxicity: beware of the association of diarrhea, drug interaction and pharmacogenetics. Pediatr Nephrol 25, 965–969 (2010). https://doi.org/10.1007/s00467-009-1402-8

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  • DOI: https://doi.org/10.1007/s00467-009-1402-8

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