Premium
Correlation Between Imatinib Pharmacokinetics and Clinical Response in Japanese Patients With Chronic‐Phase Chronic Myeloid Leukemia
Author(s) -
Takahashi N,
Wakita H,
Miura M,
Scott S A,
Nishii K,
Masuko M,
Sakai M,
Maeda Y,
Ishige K,
Kashimura M,
Fujikawa K,
Fukazawa M,
Katayama T,
Monma F,
Narita M,
Urase F,
Furukawa T,
Miyazaki Y,
Katayama N,
Sawada K
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2010.186
Subject(s) - imatinib , medicine , myeloid leukemia , imatinib mesylate , chronic myelogenous leukemia , cohort , pharmacokinetics , odds ratio , oncology , gastroenterology , leukemia
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. Clinical Pharmacology & Therapeutics (2010) 88 6, 809–813. doi: 10.1038/clpt.2010.186