title: Population Pharmacokinetics of Imatinib and its application to the therapeutic drug monitoring: Middle East CML population.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ansari
authors.affiliation: Department of Oncology and Hematology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Behjat
authors.initials: B
authors.lastname: Kalantary-Khandani
authors.affiliation: Pharmaceutics Research Center, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Pardakhty
authors.affiliation: Department of Pathology, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Moein
authors.initials: M
authors.lastname: Safavi
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nabi
authors.initials: N
authors.lastname: Mosavi
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Ehsan
authors.initials: E
authors.lastname: Mohajeri
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate / Q000493:pharmacokinetics*; D007492:Iran; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008877:Middle East; D011159:Population Surveillance
chemical_list: D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate