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Tacrolimus nephrotoxicity: beware of the association of diarrhea, drug interaction and pharmacogenetics |
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| Authors: | Sandrine Leroy Arnaud Isapof Sonia Fargue May Fakhoury Albert Bensman Georges Deschênes Evelyne Jacqz-Aigrain Tim Ulinski |
| Affiliation: | 1. Department of Pediatric Nephrology, Armand-Trousseau Hospital, AP-HP and University Paris VI, 26 Avenue du Docteur Arnold Netter, 75012, Paris, France 2. Department of Biology, University College London, London, UK 3. Department of Pediatric Nephrology—Reference Centre for Rare Renal Diseases, Femme Mère Enfant Hospital, University of Lyon, Lyon, France 4. Department of Pediatric Pharmacology—Pharmacogenetics and Clinical Investigation Center—CIC9202, Robert-Debré Hospital, AP-HP, Paris, France 5. Department of Pediatric Nephrology, Robert-Debré Hospital, AP-HP, Paris, France 6. Inserm UMR S938, Université Pierre et Marie Curie, Paris, France |
| 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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