title: Cross-sectional study of imatinib plasma trough levels in patients with advanced gastrointestinal stromal tumors: impact of gastrointestinal resection on exposure to imatinib.
abstract: OBJECTIVE
  Imatinib plasma trough levels (C(min)) have been reported to correlate with treatment outcomes in patients with gastrointestinal stromal tumors (GISTs). We therefore have evaluated the correlation between imatinib C(min) and the clinical characteristics of patients with GIST.
  
  
  METHODS
  Steady-state imatinib C(min) in 107 patients with GIST who were taking imatinib 300 to 800 mg/d was measured.
  
  
  RESULTS
  In patients treated with imatinib 400 (n = 92), 300 (n = 7), 600 (n = 2), or 800 (n = 11) mg/d, imatinib C(min) was 1,305 +/- 633 ng/mL, 1,452 +/- 830 ng/mL, 1,698 +/- 725 ng/mL, and 3,330 +/- 1,592 ng/mL, respectively. Of the 92 patients treated with 400 mg/d imatinib, 59 patients (63%) were men; the median age was 55 years (range, 28 to 76 years), and the median duration of imatinib use before sampling was 8.8 months (range, 0.5 to 67.6 months). The mean inter- and intrapatient variability rates were 44.7% and 26.5%, respectively. In univariate analyses, high C(min) was correlated with advanced age (P = .02), low creatinine clearance (P = .001), low hemoglobin (P = .03), and low albumin (P < .001) concentrations. Imatinib C(min) was also significantly lower in patients with (n = 18; 942 +/- 330 ng/mL) than without (n = 74; 1,393 +/- 659 ng/mL) major (ie, total or subtotal) gastrectomy (P = .002). In multivariate analysis, albumin (P = .001) concentrations, creatinine clearance (P = .002), and major gastrectomy (P = .003) were significantly correlated with C(min).
  
  
  CONCLUSIONS
  In patients with GIST, imatinib C(min) at steady state was significantly associated with albumin concentration, creatinine clearance, and previous major gastrectomy. Although its clinical impact is unclear at present time, monitoring of imatinib C(min) might be particularly important for optimal treatment with imatinib in patients who have undergone major gastrectomy.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Changhoon
authors.initials: C
authors.lastname: Yoo
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.forename: Byung Woog
authors.initials: BW
authors.lastname: Kang
authors.forename: Shin-Kyo
authors.initials: SK
authors.lastname: Yoon
authors.forename: Baek-Yeol
authors.initials: BY
authors.lastname: Ryoo
authors.forename: Heung-Moon
authors.initials: HM
authors.lastname: Chang
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.forename: Mo Youl
authors.initials: MY
authors.lastname: Beck
authors.forename: Tae Won
authors.initials: TW
authors.lastname: Kim
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001549:Benzamides; D003430:Cross-Sectional Studies; D005260:Female; D005743:Gastrectomy; D046152:Gastrointestinal Stromal Tumors / Q000097:blood* / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011743:Pyrimidines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate