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https://hdl.handle.net/2440/116605
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dc.contributor.author | Barratt, D. | - |
dc.contributor.author | Cox, H. | - |
dc.contributor.author | Menelaou, A. | - |
dc.contributor.author | Yeung, D. | - |
dc.contributor.author | White, D. | - |
dc.contributor.author | Hughes, T. | - |
dc.contributor.author | Somogyi, A. | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Clinical Pharmacokinetics, 2017; 56(8):977-985 | - |
dc.identifier.issn | 0312-5963 | - |
dc.identifier.issn | 1179-1926 | - |
dc.identifier.uri | http://hdl.handle.net/2440/116605 | - |
dc.description.abstract | Objective: The 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. Methods: 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). Results: 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). Conclusions: CYP2C8 genotype significantly alters imatinib metabolism in patients through gain- and loss-of-function mechanisms. | - |
dc.description.statementofresponsibility | Daniel T. Barratt, Hannah K. Cox, Andrew Menelaou, David T. Yeung, Deborah L. White, Timothy P. Hughes, Andrew A. Somogyi | - |
dc.language.iso | en | - |
dc.publisher | Springer | - |
dc.rights | © Springer International Publishing Switzerland 2016. | - |
dc.source.uri | http://dx.doi.org/10.1007/s40262-016-0494-0 | - |
dc.subject | Imatinib; human liver microsome; chronic myeloid leukaemia patient; metabolic ratio; systemic mastocytosis | - |
dc.title | CYP2C8 genotype significantly alters imatinib metabolism in chronic myeloid leukaemia patients | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1007/s40262-016-0494-0 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Barratt, D. [0000-0001-6261-353X] | - |
dc.identifier.orcid | Yeung, D. [0000-0002-7558-9927] | - |
dc.identifier.orcid | White, D. [0000-0003-4844-333X] | - |
dc.identifier.orcid | Hughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509] | - |
dc.identifier.orcid | Somogyi, A. [0000-0003-4779-0380] | - |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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