title: Tacrolimus nephrotoxicity: beware of the association of diarrhea, drug interaction and pharmacogenetics.
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.
authors.affiliation: Department of Pediatric Nephrology, Armand-Trousseau Hospital, AP-HP and University Paris VI, 26 Avenue du Docteur Arnold Netter, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Leroy
authors.forename: Arnaud
authors.initials: A
authors.lastname: Isapof
authors.forename: Sonia
authors.initials: S
authors.lastname: Fargue
authors.forename: May
authors.initials: M
authors.lastname: Fakhoury
authors.forename: Albert
authors.initials: A
authors.lastname: Bensman
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jacqz-Aigrain
authors.forename: Tim
authors.initials: T
authors.lastname: Ulinski
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics; D000293:Adolescent; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D003967:Diarrhea / Q000150:complications*; D004347:Drug Interactions; D016903:Drug Monitoring; D020022:Genetic Predisposition to Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D016030:Kidney Transplantation; D008297:Male; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus