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The Role of Therapeutic Drug Monitoring of Imatinib in Patients with Chronic Myeloid Leukemia and Metastatic or Unresectable Gastrointestinal Stromal Tumors.
MedLine Citation:
PMID:  22215488     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
ABSTRACT:: Imatinib mesylate is a tyrosine kinase inhibitor used as first-line treatment in Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) and metastatic or unresectable gastrointestinal stromal tumors (GIST). Therapeutic drug monitoring (TDM) for imatinib has been suggested to improve efficacy, assess compliance, and evaluate drug-drug interactions. Imatinib has proven efficacy in improving treatment response and survival in patients with Ph+ CML and GIST. Several analytical methods are available to quantify total plasma imatinib concentrations. A good relationship exists between total imatinib plasma concentrations and pharmacologic response. Clinical evaluation of pharmacologic response to imatinib alone may be insufficient given the long duration of therapy before clinical response in patients with Ph+ CML and GIST. Thus, the authors have used a previously published 9-step decision-making algorithm to evaluate the utility of TDM for imatinib. The suggested trough concentrations for improved complete cytogenetic or major molecular response in patients with Ph+ CML and improved time to progression for patients with GIST are >1000 and >1100 ng/mL, respectively. Imatinib exhibits interindividual pharmacokinetic variability. Increased apparent clearance of imatinib has been observed in chronic phase chronic myeloid leukemia and increased body weight. Decreased apparent clearance has been observed in renal impairment and patients on concomitant medications with potent inhibition of cytochrome P450 3A4. Duration of therapy in patients with Ph+ CML and GIST is lifelong. Based on the available evidence, TDM for imatinib may provide additional information on efficacy, compliance, and safety than clinical evaluation alone. Patients with suboptimal response to treatment, treatment failure, rare adverse events, drug interactions, or suspected nonadherence will attain the greatest benefit from TDM.
Authors:
Jennifer F T Teng; Vincent H Mabasa; Mary H H Ensom
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-30
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  -     ISSN:  1536-3694     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
From the *Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver; †Department of Pharmacy, Burnaby General Hospital, Burnaby; and ‡Department of Pharmacy, Children's and Women's Health Centre of British Columbia, Vancouver, Canada.
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