title: Calcium carbonate does not affect imatinib pharmacokinetics in healthy volunteers.
abstract: OBJECTIVE
  Imatinib mesylate (Gleevec(®)/Glivec(®)) has revolutionized the treatment of chronic myeloid leukemias and gastrointestinal stromal tumors, and there is evidence for an exposure response relationship. Calcium carbonate is increasingly used as a calcium supplement and in the setting of gastric upset associated with imatinib therapy. Calcium carbonate could conceivably elevate gastric pH and complex imatinib, thereby influencing imatinib absorption and exposure. We aimed to evaluate whether use of calcium carbonate has a significant effect on imatinib pharmacokinetics.
  
  
  METHODS
  Eleven healthy subjects were enrolled in a 2-period, open-label, single-institution, randomized crossover, fixed-schedule study. In one period, each subject received 400 mg of imatinib p.o. In the other period, 4,000 mg calcium carbonate (Tums Ultra(®)) was administered p.o. 15 min before 400 mg of imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite CGP74588 were assayed by LC-MS; data were analyzed non-compartmentally and compared after log transformation.
  
  
  RESULTS
  Calcium carbonate administration did not significantly affect the imatinib area under the plasma concentration versus time curve (AUC) (41.2 μg/mL h alone vs. 40.8 μg/mL h with calcium carbonate, P = 0.99), maximum plasma concentration (C(max)) (2.35 μg/mL alone vs. 2.39 μg/mL with calcium carbonate, P = 0.89).
  
  
  CONCLUSIONS
  Our results indicate that the use of calcium carbonate does not significantly affect imatinib pharmacokinetics.
authors.affiliation: Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Room G27E, 5117 Centre Avenue, Pittsburgh, PA, 15213-1863, USA.
authors.forename: Hussein
authors.initials: H
authors.lastname: Tawbi
authors.forename: Susan M
authors.initials: SM
authors.lastname: Christner
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Matthew
authors.initials: M
authors.lastname: Johnson
authors.forename: Emily T
authors.initials: ET
authors.lastname: Mowrey
authors.forename: Craig
authors.initials: C
authors.lastname: Cherrin
authors.forename: Edward
authors.initials: E
authors.lastname: Chu
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Shannon
authors.initials: S
authors.lastname: Puhalla
authors.forename: Ronald
authors.initials: R
authors.lastname: Stoller
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Appleman
authors.forename: Brian M
authors.initials: BM
authors.lastname: Miller
authors.forename: Jan H
authors.initials: JH
authors.lastname: Beumer
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001549:Benzamides / Q000493:pharmacokinetics*; D002119:Calcium Carbonate / Q000494:pharmacology*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D002119:Calcium Carbonate