The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes.

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dc.contributor.author Helsby, Nuala en
dc.contributor.author Yong, M en
dc.contributor.author van Kan, Maia en
dc.contributor.author de Zoysa, Janak en
dc.contributor.author Burns, Kathryn en
dc.date.accessioned 2019-10-01T21:08:59Z en
dc.date.issued 2019-09 en
dc.identifier.issn 0306-5251 en
dc.identifier.uri http://hdl.handle.net/2292/48310 en
dc.description.abstract Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for the role of germline pharmacogenetic variation in both plasma pharmacokinetics and clinical outcomes. There is a substantial indication from 13 pharmacokinetic and 17 therapeutic outcome studies, in contexts as diverse as haematological malignancy, breast cancer, systemic lupus erythematosus and myeloablation, that pharmacogenetic variation in both CYP2C19 and CYP2B6 influence the bioactivation of cyclophosphamide. An additional role for pharmacogenetic variation in ALDH1A1 has also been reported. Future studies should comprehensively assess these 3 pharmacogenes and undertake appropriate statistical analysis of gene-gene interactions to confirm these findings and may allow personalised treatment regimens. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries British journal of clinical pharmacology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes. en
dc.type Journal Article en
dc.identifier.doi 10.1111/bcp.14031 en
pubs.issue 9 en
pubs.begin-page 1925 en
pubs.volume 85 en
dc.rights.holder Copyright: The author en
pubs.end-page 1934 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Review en
pubs.subtype Journal Article en
pubs.elements-id 775421 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Molecular Medicine en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1365-2125 en
pubs.record-created-at-source-date 2019-06-21 en
pubs.dimensions-id 31218720 en


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