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

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. Keywords Calcium channel blocker * Cytochrome P450 * Diarrhoea * P-glycoprotein * Polymorphisms * Renal transplant * Tacrolimus
Introduction Tacrolimus is a calcineurin inhibitor increasingly used for immunosuppression in renal transplantation [1]. Following oral administration, tacrolimus is preferentially absorbed in the duodenum and jejunum with highly variable pharmacokinetics [...]