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Please use this identifier to cite or link to this item: https://hdl.handle.net/11055/456
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dc.contributor.authorBarratt, Daniel T
dc.contributor.authorCox, Hannah K
dc.contributor.authorMenelaou, Andrew
dc.contributor.authorYeung, David T
dc.contributor.authorWhite, Deborah L
dc.contributor.authorHughes, Timothy P
dc.contributor.authorSomogyi, Andrew A
dc.date.accessioned2018-04-08T01:03:49Z-
dc.date.available2018-04-08T01:03:49Z-
dc.date.issued2017-08
dc.identifier.citationClinical pharmacokinetics 2017-08; 56(8): 977-985
dc.identifier.urihttp://hdl.handle.net/11055/456-
dc.description.abstractThe aims of this study were to determine the effects of the CYP2C8*3 and *4 polymorphisms on imatinib metabolism and plasma imatinib concentrations in chronic myeloid leukaemia (CML) patients. We genotyped 210 CML patients from the TIDELII trial receiving imatinib 400-800 mg/day for CYP2C8*3 (rs11572080, rs10509681) and *4 (rs1058930). Steady-state trough total plasma N-desmethyl imatinib (major metabolite):imatinib concentration ratios (metabolic ratios) and trough total plasma imatinib concentrations were compared between genotypes (one-way ANOVA with Tukey post hoc). CYP2C8*3 (n = 34) and *4 (n = 15) carriers had significantly higher (P < 0.01) and lower (P < 0.01) metabolic ratios, respectively, than CYP2C8*1/*1 (n = 147) patients (median ± standard deviation: 0.28 ± 0.08, 0.18 ± 0.06 and 0.22 ± 0.08, respectively). Plasma imatinib concentrations were consequently > 50% higher for CYP2C8*1/*4 than for CYP2C8*1/*1 and CYP2C8*3 carriers (2.18 ± 0.66 vs. 1.45 ± 0.74 [P < 0.05] and 1.36 ± 0.98 μg/mL [P < 0.05], respectively). CYP2C8 genotype significantly alters imatinib metabolism in patients through gain- and loss-of-function mechanisms.
dc.language.isoeng
dc.titleCYP2C8 Genotype Significantly Alters Imatinib Metabolism in Chronic Myeloid Leukaemia Patients.
dc.typeJournal Article
dc.identifier.journaltitleClinical pharmacokinetics
dc.identifier.doi10.1007/s40262-016-0494-0
dc.description.pubmedurihttps://www.ncbi.nlm.nih.gov/pubmed/27995529
dc.identifier.pubmedid27995529
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
Appears in Collections:Scholarly and Clinical
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