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Population Pharmacokinetics of Imatinib and Its Application to the Therapeutic Drug Monitoring: Middle East Cml Population Pubmed



Ansari M1 ; Kalantarykhandani B2 ; Pardakhty A3 ; Safavi M4 ; Mosavi N5 ; Mohajeri E1
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
  2. 2. Department of Oncology and Hematology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
  3. 3. Pharmaceutics Research Center, Kerman University of Medical Sciences, Kerman, Iran
  4. 4. Department of Pathology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
  5. 5. Department of Medical Oncology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: The Gulf journal of oncology Published:2016


Abstract

INTRODUCTION: Despite the outstanding results generally obtained with Imatinib in the treatment of chronic myeloid leukemia, some patients show sub-optimal or no response. To evaluate the relationship between steady-state through plasma concentration and clinical response in CML patients. The objectives of this study were to assess the variability in Imatinib pharmacokinetics and to explore the effects of several demographic and biological covariates on the disposition of Imatinib.; METHODS: A population pharmacokinetic analysis was performed on 170 plasma samples from 74 adult Iranian chronic myeloid leukemia patients. A population pharmacokinetics model was developed to evaluate the influence of covariates on clearance and volume of distribution.; RESULTS: A one-compartment model with first-order absorption appropriately described the data, giving a mean (±SEM) clearance of 14.3l (±1.0) and a volume of distribution of 347 l (±62). Clearance was influenced by body weight, age and gender. By considering these covariates the interindividual variability decreased from 47% to 19%. A large proportion of the interindividual variability (19% of clearance and 45% of volume of distribution) remained unexplained by these demographic covariates.; DISCUSSION AND CONCLUSION: By considering morphological and biological covariates, a unique covariate model could be used to accurately describe Imatinib pharmacokinetics in our population and because of the pharmacokinetic variability of Imatinib and the reported relationships between its plasma concentration and efficacy and toxicity, the usefulness of therapeutic drug monitoring as an aid to optimizing therapy should be further investigated.