title: A case of severe toxicity during coadministration of vincristine and piperacillin:  are drug transporters involved in vincristine hypersensitivity and drug-drug interactions?
abstract: Neurotoxicity is frequent with vincristine treatment, but severe autonomic neuropathy is rare. A decreased activity of drug transporters in the presence of an interacting drug may favor such events by increasing systemic or tissue exposure to the drug. We encountered severe autonomic neuropathy and cholestasis in a child receiving vincristine, after the introduction of piperacillin-tazobactam. A causality assessment of the adverse reaction identified the antibiotic as the most probable cause of the observation. The patient was heterozygous for several common polymorphisms of ABCC2 (multidrug-related protein-2), CYP3A5, and ABCB1 (multidrug-related protein-1, P-glycoprotein), but their role in the toxicity cannot be ascertained.
authors.affiliation: Department of Pharmacology, Faculté de Médecine, Université François Rabelais, Tours, France. leguellec@med.univ-tours.fr
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Guellec
authors.forename: Isabelle
authors.initials: I
authors.lastname: Benz-de Bretagne
authors.forename: Annie-Pierre
authors.initials: AP
authors.lastname: Jonville-Bera
authors.forename: Naoual
authors.initials: N
authors.lastname: Tarfaoui
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.forename: Chantal
authors.initials: C
authors.lastname: Gendrot
authors.forename: Anne
authors.initials: A
authors.lastname: Jourdain
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000502:physiology; D015746:Abdominal Pain / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics; D001215:Asparaginase / Q000008:administration & dosage; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy; D001692:Biological Transport; D002648:Child; D002779:Cholestasis / Q000139:chemically induced*; D003520:Cyclophosphamide / Q000008:administration & dosage; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000502:physiology; D003630:Daunorubicin / Q000008:administration & dosage; D004338:Drug Combinations; D004347:Drug Interactions; D005157:Facial Pain / Q000139:chemically induced; D005260:Female; D006801:Humans; D007415:Intestinal Obstruction / Q000209:etiology; D007418:Intestinal Pseudo-Obstruction / Q000209:etiology; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000502:physiology; D009266:Nalbuphine / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D009437:Neuralgia / Q000139:chemically induced* / Q000188:drug therapy; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D000078142:Tazobactam; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001215:Asparaginase; D003520:Cyclophosphamide; D051544:Cytochrome P-450 CYP3A; D003630:Daunorubicin; D004338:Drug Combinations; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009266:Nalbuphine; D009363:Neoplasm Proteins; D010397:Penicillanic Acid; D010878:Piperacillin; D011241:Prednisone; D000078142:Tazobactam; D014750:Vincristine; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C510164:CYP3A5 protein, human