Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients

Title
Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients
Author(s)
현명수Y.-R. Yoon[Y.-R. Yoon]S. J. Seong[S. J. Seong]M. Lim[M. Lim]S. K. Sohn[S. K. Sohn]J. H. Moon[J. H. Moon]S.-J. Oh[S.-J. Oh]B. S. Kim[B. S. Kim]H. M. Ryoo[H. M. Ryoo]김민경임미선S. J. Seong[S. J. Seong]S. K. Sohn[S. K. Sohn]J. H. Moon[J. H. Moon]S.-J. Oh[S.-J. Oh]B. S. Kim[B. S. Kim]H. M. Ryoo[H. M. Ryoo]J. S. Chung[J. S. Chung]Y. D. Joo[Y. D. Joo]S. M. Bang[S. M. Bang]C. W. Jung[C. W. Jung]D. H. Kim[D. H. Kim]S. Y. Park[S. Y. Park]S. S. Yoon[S. S. Yoon]I. Kim[I. Kim]H. G. Lee[H. G. Lee]J. H. Won[J. H. Won]Y. H. Min[Y. H. Min]J. W. Cheong[J. W. Cheong]J. S. Park[J. S. Park]K. S. Eom[K. S. Eom]M. S. Hyun[M. S. Hyun]M. K. Kim[M. K. Kim]H. Kim[H. Kim]M. R. Park[M. R. Park]J. Park[J. Park]C. S. Kim[C. S. Kim]H. J. Kim[H. J. Kim]Y. K. Kim[Y. K. Kim]E. K. Park[E. K. Park]D. Y. Zang[D. Y. Zang]D. Y. Jo[D. Y. Jo]H. W. Lee[H. W. Lee]Y.-R. Yoon[Y.-R. Yoon]
Keywords
MOLECULAR RESPONSES; ABCB1 MDR1; PHARMACOKINETICS; MESYLATE; THERAPY; RESISTANCE; PLASMA; DISPOSITION; FAILURE
Issue Date
201303
Publisher
OXFORD UNIV PRESS
Citation
ANNALS OF ONCOLOGY, v.24, no.3, pp.756 - 760
Abstract
Background: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). Patients and methods: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. Results: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. Conclusions: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.
URI
http://hdl.handle.net/YU.REPOSITORY/26269http://dx.doi.org/10.1093/annonc/mds532
ISSN
0923-7534
Appears in Collections:
의과대학 > 내과학교실 > Articles
약학대학 > 약학부 > Articles
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