Drug intelligence / Profile preview

dasatinib + rabeprazole + betaine hydrochloride

Development stage
Phase 1
Lead developer
Bristol Myers Squibb
Modality
Small Molecules
Administration
Oral
01

Overview

This is a combination of three agents: dasatinib, rabeprazole, and betaine hydrochloride. Dasatinib is an oral second-generation small molecule tyrosine kinase inhibitor primarily used for the treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). It inhibits BCR-ABL, SRC family kinases, c-KIT, EPHA2, and PDGFRβ. Rabeprazole is a proton pump inhibitor that suppresses gastric acid secretion by inhibiting the H+/K+ ATPase in gastric parietal cells; it is used to treat conditions like gastroesophageal reflux disease but can reduce the absorption of drugs with pH-dependent solubility such as dasatinib. Betaine hydrochloride (BHCl) is an acidic supplement that transiently re-acidifies gastric pH after acid suppression by agents like rabeprazole. In clinical studies, coadministration of BHCl with dasatinib in subjects pretreated with rabeprazole restored dasatinib absorption to levels comparable to administration without acid suppression[1][2][7]. This combination has been studied as a strategy to mitigate drug-drug interactions between oral anticancer drugs requiring acidic environments for optimal absorption and concurrent use of acid-reducing agents.

Brand names
Acidil
Other names
BHCl
02

Targets

ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)EPHA2 (Ephrin type-A receptor 2)ATP4A (Potassium–transporting ATPase alpha chain 1)PDGFRB (Platelet-derived growth factor receptor beta)SFK (SRC family kinases)KIT (c-KIT proto-oncogene receptor tyrosine kinase)

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