Dasatinib anhydrate containing oral formulation improves variability and bioavailability in humans

Area of Science:

• Pharmacology
• Drug Development

Background:

• Dasatinib monohydrate, used for chronic myeloid leukemia (CML), exhibits pH-dependent solubility.
• Proton pump inhibitors (PPIs) are frequently co-prescribed with dasatinib despite warnings, highlighting formulation challenges.

Purpose of the Study:

• To develop a novel dasatinib anhydrate formulation with improved absorption and reduced pharmacokinetic variability.
• To compare the bioavailability and drug-drug interaction profile of the new formulation against dasatinib monohydrate.

Main Methods:

• A bioavailability study compared dasatinib anhydrate (110.6 mg) and monohydrate (140 mg) formulations.
• A drug-drug interaction study assessed the effect of omeprazole on dasatinib exposure.
• Co-prescription analysis examined dasatinib use with PPIs.

Main Results:

• Both formulations achieved Cmax and AUC within the standard range.
• The dasatinib anhydrate formulation showed approximately 3-fold lower intra-subject and 1.5-fold lower inter-subject variability for AUC0-inf.
• Omeprazole reduced dasatinib AUC0-inf by 19%, a clinically irrelevant decrease, and less than observed with the monohydrate form.

Conclusions:

• The novel dasatinib anhydrate formulation offers improved absorption and pharmacokinetic stability over the monohydrate form.
• These improvements may translate to enhanced clinical efficacy, warranting further investigation in clinical trials.