Please use this identifier to cite or link to this item:
|Title:||CYP2C8 Genotype Significantly Alters Imatinib Metabolism in Chronic Myeloid Leukaemia Patients.|
|Authors:||Barratt, Daniel T|
Cox, Hannah K
Yeung, David T
White, Deborah L
Hughes, Timothy P
Somogyi, Andrew A
|Citation:||Clinical pharmacokinetics 2017-08; 56(8): 977-985|
|Abstract:||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. 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.|
|Journal Title:||Clinical pharmacokinetics|
|Appears in Collections:||Scholarly and Clinical|
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.