title: Correlation between imatinib pharmacokinetics and clinical response in Japanese patients with chronic-phase chronic myeloid leukemia.
abstract: Despite the outstanding results generally obtained with imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), some patients show a poor molecular response. To evaluate the relationship between steady-state trough plasma IM concentration (IM-C(min)) and clinical response in CML patients, we integrated data from six independent Japanese studies. Among 254 CML patients, the mean IM-C(min) was 1,010.5 ng/ml. Importantly, IM-C(min) was significantly higher in patients who achieved a major molecular response (MMR) than in those who did not (P = 0.002). Multivariate analysis showed that an MMR was associated with both age (odds ratio (OR) = 0.97 (0.958-0.995); P = 0.0153) and with IM-C(min) (OR = 1.0008 (1.0003-1.0015); P = 0.0044). Given that patients with IM-C(min) values >1,002 ng/ml had a higher probability of achieving an MMR in our large cohort (P = 0.0120), the data suggest that monitoring of IM levels in plasma may improve the efficacy of IM therapy for CML patients.
authors.affiliation: Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan. naotot@doc.med.akita-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Wakita
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: S A
authors.initials: SA
authors.lastname: Scott
authors.forename: K
authors.initials: K
authors.lastname: Nishii
authors.forename: M
authors.initials: M
authors.lastname: Masuko
authors.forename: M
authors.initials: M
authors.lastname: Sakai
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: K
authors.initials: K
authors.lastname: Ishige
authors.forename: M
authors.initials: M
authors.lastname: Kashimura
authors.forename: K
authors.initials: K
authors.lastname: Fujikawa
authors.forename: M
authors.initials: M
authors.lastname: Fukazawa
authors.forename: T
authors.initials: T
authors.lastname: Katayama
authors.forename: F
authors.initials: F
authors.lastname: Monma
authors.forename: M
authors.initials: M
authors.lastname: Narita
authors.forename: F
authors.initials: F
authors.lastname: Urase
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: N
authors.initials: N
authors.lastname: Katayama
authors.forename: K
authors.initials: K
authors.lastname: Sawada
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D001549:Benzamides; D015331:Cohort Studies; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate