Tacrolimus Nephrotoxicity: Beware of the Association of Diarrhea, Drug Interaction and Pharmacogenetics

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2010 Jan 22

PMID 20091056

Citations 11

Authors

Sandrine Leroy

Arnaud Isapof

Sonia Fargue

May Fakhoury

Albert Bensman

Georges Deschenes

Evelyne Jacqz-Aigrain

Tim Ulinski

Affiliations

Soon will be listed here.

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.

Citing Articles

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