New bedaquiline salt with improved bioavailability and reduced food effect

Bedaquiline (BDQ) is an orally administered diarylquinoline class anti-tuberculosis drug used in the combination therapy of MDR-TB. Currently, it is marketed as bedaquiline fumarate (BDQ–FA). However, due to its poor water solubility, BDQ–FA must be taken with food to enhance bioavailability. Concurrent administration reduces patient compliance and may increase the risk of inconsistent serum levels due to differences in dietary habits. This study designed and synthesized the saccharin salt of bedaquiline (BDQ–SA). Compared to the marketed fumarate salt, BDQ–SA exhibits better solubility and absorption. The food effect of commercially available BDQ–FA in beagle dogs was 7.2 times, while that of BDQ–SA was 3.2 times. This study provides a good example of using a new salt form to improve drug solubility and mitigate the food effect of the drug.