Purpose: Imatinib often causes gastric upset resulting in frequent co-administration of an antacid. Elevated gastric pH, delayed gastric emptying, or introduction of Mg(2+)/Al(3+) 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 microg/(mL h) alone versus 32.6 microg/(mL h) with antacid, P = 0.37; 80% power].
Conclusions: Our results indicate that the use of Mg(2+)-Al(3+)-based antacid does not significantly affect imatinib absorption.