Cancer Chemotherapy and Pharmacology

, Volume 63, Issue 3, pp 525–528

Effect of antacid on imatinib absorption

  • Brian A. Sparano
  • Merrill J. Egorin
  • Robert A. Parise
  • Jennifer Walters
  • Kristin A. Komazec
  • Robert L. Redner
  • Jan H. Beumer
Original Article

Abstract

Purpose

Imatinib often causes gastric upset resulting in frequent co-administration of an antacid. Elevated gastric pH, delayed gastric emptying, or introduction of Mg2+/Al3+ could potentially change imatinib absorption, thereby affecting the therapeutic effectiveness of imatinib. Indeed, antacid co-administration with dasatinib does result in a twofold decrease in dasatinib absorption. We aimed to define the effect of antacid on the pharmacokinetics of imatinib.

Methods

Twelve healthy subjects were enrolled in a 2-period, open-label, randomized cross-over, fixed-sequence study. In one period, each subject received 400 mg imatinib p.o., and in the other, the same dose of imatinib preceded by 20 mL antacid, containing 1.6 g Al(OH)3 + 1.6 g Mg(OH)2, 15 min before imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite CGP74588 were determined by LC–MS, and data were analyzed non-compartmentally.

Results

Antacid administration did not significantly affect the area under the plasma imatinib concentration versus time curve (AUC) [31.7 μg/(mL h) alone versus 32.6 μg/(mL h) with antacid, = 0.37; 80% power].

Conclusions

Our results indicate that the use of Mg2+-Al3+-based antacid does not significantly affect imatinib absorption.

Keywords

Imatinib CML GIST Interaction 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Brian A. Sparano
    • 1
  • Merrill J. Egorin
    • 1
    • 2
    • 3
  • Robert A. Parise
    • 2
    • 4
  • Jennifer Walters
    • 5
  • Kristin A. Komazec
    • 5
  • Robert L. Redner
    • 1
  • Jan H. Beumer
    • 2
    • 4
  1. 1.Division of Hematology/Oncology, Department of MedicineUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Molecular Therapeutics/Drug Discovery ProgramUniversity of Pittsburgh Cancer InstitutePittsburghUSA
  3. 3.Department of PharmacologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of Pharmaceutical SciencesUniversity of Pittsburgh School of PharmacyPittsburghUSA
  5. 5.Clinical Research ServicesUniversity of Pittsburgh Cancer InstitutePittsburghUSA

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