Influence of H2-receptor antagonists and proton pump inhibitors on dasatinib pharmacokinetics in Japanese leukemia patients
Abstract
PURPOSE: The objective of this study was to investigate the drug interaction between dasatinib and the gastric acid suppressants (H2-receptor antagonists (H2RA) famotidine and nizatidine and the proton pump inhibitor (PPI) lansoprazole in leukemia Japanese patients.
METHODS: Eighteen patients treated with dasatinib and H2RA, PPI or no acid suppressant from whom were obtained a total of 34 pharmacokinetic profiles were enrolled in the study. Dasatinib plasma concentrations from samples obtained just prior to and 1, 2, and 4 h after oral dasatinib administration were analyzed by high-performance liquid chromatography.
RESULTS: There were no significant correlations between the dose-adjusted total area under the observed plasma concentration-time curve (AUC(0-4)) of dasatinib and gender, age, weight, or body surface area. The only variable factor, the dasatinib dose-adjusted AUC(0-4) for patients administered an H2RA or PPI, was significantly lower than for patients not administered an acid suppressant (median (quartile 1-quartile 3) values: 1.47 (0.79-2.29) versus 3.51 (2.50-5.45) ng h/mL/mg, respectively, P = 0.0008). Moreover, the plasma concentration 2 h (C(2h)) after dasatinib administration gave a high correlation with the AUC(0-4) of dasatinib (r = 0.9419, P < 0.0001).
CONCLUSION: Clinicians should be aware that administration of an acid suppressant such as famotidine, nizatidine, and lansoprazole can decrease the absorption of dasatinib from the gastrointestinal tract,…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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