title: Plasma and intracellular imatinib concentrations in patients with chronic myeloid leukemia.
abstract: BACKGROUND
  Imatinib (Gleevec, STI-571), a 2-phenylaminopyrimidine-type competitive inhibitor of Bcr-Abl kinase, is the current frontline therapy for patients with chronic myeloid leukemia, and it induces durable responses and prolonging event-free and progression-free survival. Monitoring imatinib trough plasma concentration is a simple and rapid way to determine if the drug exposure exceeds the clinical efficacy threshold (1 mcg/mL). Because the target enzyme is located within cells, adequate drug intracellular concentrations are needed to inhibit its function.
  
  
  METHODS
  Chromatographic methods were used to quantify imatinib concentrations in both plasma and peripheral blood mononuclear cells collected from adult patients with chronic myeloid leukemia at the Department of Hematology. Samples were collected at steady state, and trough concentrations (24 ± 2 hours after last drug intake) were evaluated. Associations between variables were tested using the Pearson test; results are presented as mean (±SD).
  
  
  RESULTS
  Thirty-five samples from 24 patients were collected; patients were mainly men (16, 66.7%), aged 60 years old (±13.1) and with a body mass index of 24.8 (±4.4). A positive and significant correlation (r = 0.203; P = 0.027) was found between imatinib plasma and intracellular concentrations.
  
  
  CONCLUSIONS
  The observed correlation between plasma and intracellular imatinib concentrations suggests that they may be used to monitor drug exposure and treatment efficacy.
authors.affiliation: *Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy; and †Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: De Francia
authors.forename: Antonio
authors.initials: A
authors.lastname: DʼAvolio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ariaudo
authors.forename: Elisa
authors.initials: E
authors.lastname: Pirro
authors.forename: Francesca
authors.initials: F
authors.lastname: Piccione
authors.forename: Marco
authors.initials: M
authors.lastname: Simiele
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.forename: Andrea
authors.initials: A
authors.lastname: Calcagno
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001549:Benzamides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015992:Body Mass Index; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010949:Plasma / Q000737:chemistry; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate