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Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia.
MedLine Citation:
PMID:  20720558     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Imatinib mesylate (IM) trough concentration varies among IM-treated chronic myeloid leukemia (CML) patients. Although IM pharmacokinetics is influenced by several enzymes and transporters, little is known about the role of pharmacogenetic variation in IM metabolism. In this study, associations between IM trough concentration, clinical response and 11 single-nucleotide polymorphisms in genes involved in IM pharmacokinetics (ABCB1, ABCC2, ABCG2 CYP3A5, SLC22A1 and SLCO1B3) were investigated among 67 Japanese chronic phase CML patients. IM trough concentration was significantly higher in patients with a major molecular response than in those without one (P=0.010). No significant correlations between IM trough concentration and age, weight, body mass index or biochemical data were observed. However, the dose-adjusted IM trough concentration was significantly higher in patients with ABCG2 421A than in those with 421C/C (P=0.015). By multivariate regression analysis, only ABCG2 421A was independently predictive of a higher dose-adjusted IM trough concentration (P=0.015). Moreover, previous studies have shown that the ABCG2 421C>A (p.Q141K) variant is prevalent among Japanese and Han Chinese individuals and less common among Africans and Caucasians. Together, these data indicate that plasma IM concentration monitoring and prospective ABCG2 421C>A genotyping may improve the efficacy of IM therapy, particularly among Asian CML patients.
Authors:
Naoto Takahashi; Masatomo Miura; Stuart A Scott; Hideaki Kagaya; Yoshihiro Kameoka; Hiroyuki Tagawa; Hirobumi Saitoh; Naohito Fujishima; Tomoko Yoshioka; Makoto Hirokawa; Kenichi Sawada
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Publication Detail:
Type:  Journal Article     Date:  2010-08-19
Journal Detail:
Title:  Journal of human genetics     Volume:  55     ISSN:  1435-232X     ISO Abbreviation:  J. Hum. Genet.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9808008     Medline TA:  J Hum Genet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  731-7     Citation Subset:  IM    
Affiliation:
Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.
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