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Lookup NU author(s): Dr Shelby BarnettORCiD, Dr Martin Galler, Dr David Jamieson, Professor Gareth Veal
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s).Background: Dubin–Johnson syndrome is a rare benign autosomal recessive condition that causes an isolated increase of conjugated bilirubin in the serum. Impaired biliary excretion is due to mutation in the multiple drug-resistance protein 2 gene (MRP2). Case presentation: We describe the case of a 4-year-old girl being treated for acute lymphoblastic leukaemia who had a history of conjugated hyperbilirubinaemia and persistently elevated bilirubin levels on initiation of chemotherapy. During treatment for leukaemia, she was diagnosed with Dubin–Johnson syndrome for the underlying condition. Following administration of vincristine at the recommended dose of 1.5 mg/m2, an abnormally high vincristine exposure was observed (AUC > 200 µg/L*h), approximately 3 times higher than previously reported exposures in a comparable clinical setting. Vincristine dose reductions were applied on subsequent cycles of treatment and resulted in markedly reduced drug exposures, within the normal target range. Conclusion: This case provided a rare opportunity to assess the impact of MRP2 mutations associated with Dubin–Johnson syndrome on the pharmacokinetics of vincristine and strongly indicates that a marked dose reduction should be recommended. Clinicians should be made aware of the potential for altered drug disposition for agents such as vincristine in patients with this rare genetic condition.
Author(s): Barnett S, Nyein AC, Galler M, Jamieson D, Davies M, Connor P, Veal GJ
Publication type: Article
Publication status: Published
Journal: Cancer Chemotherapy and Pharmacology
Year: 2023
Volume: 92
Pages: 325–328
Online publication date: 15/07/2023
Acceptance date: 01/07/2023
Date deposited: 08/08/2023
ISSN (print): 0344-5704
ISSN (electronic): 1432-0843
Publisher: Springer Science and Business Media Deutschland GmbH
URL: https://doi.org/10.1007/s00280-023-04565-0
DOI: 10.1007/s00280-023-04565-0
PubMed id: 37452859
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