Effect of antacid on imatinib absorption.
OBJECTIVE
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.
Sparano
Brian A
BA
Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, PA 15213, USA.
Egorin
Merrill J
MJ
Parise
Robert A
RA
Walters
Jennifer
J
Komazec
Kristin A
KA
Redner
Robert L
RL
Beumer
Jan H
JH
D000328:Adult; D000863:Antacids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001549:Benzamides; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics*
D000863:Antacids; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate