Dasatinib is a tyrosine kinase inhibitor (including BCR-ABL and the SRC family) that is effective in patients with chronic myeloid leukemia. Dasatinib has pH-dependent solubility and is bioavailable as an oral formulation. The effect of gastric pH modifiers on dasatinib pharmacokinetics is evaluated in an open-label, randomized, 3-period, 3-treatment crossover study. Twenty-four healthy subjects receive treatment A (2 doses of dasatinib 50 mg separated by 12 hours), treatment B (famotidine 40 mg given 2 hours after dasatinib 50 mg and 10 hours before another dose of dasatinib 50 mg), and treatment C (30 mL of an antacid containing aluminum/magnesium hydroxides given 2 hours before dasatinib 50 mg and concomitantly with dasatinib 50 mg 12 hours after the previous dasatinib dose); a 7-day washout separates each treatment period. When famotidine is administered 2 hours after dasatinib, dasatinib exposure is similar to dasatinib administered alone. However, dasatinib exposure is reduced by ∼60% when famotidine is administered 10 hours before dasatinib dosing. In contrast, dasatinib exposure is unchanged when antacid (Maalox) is administered 2 hours before dasatinib; but when the antacid is coadministered with dasatinib, dasatinib exposure is reduced by ∼55% to 58%. This indicates that H2-receptor antagonists should not be coadministered with dasatinib. Dasatinib may be administered with acid-neutralizing antacids if the doses are temporally separated by at least 2 hours.