title: Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.
abstract: BACKGROUND
  Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea.
  
  
  OBJECTIVE
  The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers.
  
  
  METHODS
  This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞) were within the predetermined range of 0.80 - 1.25.
  
  
  RESULTS
  In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞) of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25.
  
  
  CONCLUSIONS
  The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Seong
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Park
authors.forename: Joomi
authors.initials: J
authors.lastname: Lee
authors.forename: Mi-Ri
authors.initials: MR
authors.lastname: Gwon
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sung Mook
authors.initials: SM
authors.lastname: Lim
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Lim
authors.forename: Woomi
authors.initials: W
authors.lastname: Kim
authors.forename: Dong Heon
authors.initials: DH
authors.lastname: Yang
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D016903:Drug Monitoring; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D056910:Republic of Korea; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013607:Tablets; D000068877:Imatinib Mesylate