Linerixibat

The zwitterionic, nonhygroscopic, crystalline salt form of Linerixibat shows good aqueous solubility at pH 7.4 (>7 mg/mL), excellent thermal stability, and does not generate reactive or humanspecific metabolite, characteristics.^[3]

HMDR1-MDCK cells are seeded at 6.6 × 105 cells/well onto 12-well polycarbonate Transwells filter membranes with 0.4 μm pore size. After three days, media is removed from both the apical and basolateral chambers and replaced with transport buffer (HBSS containing 25 mM glucose and 25 mM HEPES) containing the P-gp inhibitor GF120918A at a final concentration of 2 μM. After a 30 min equilibration, the transport buffer is removed from the apical chambers and replaced with fastedstate simulated intestinal fluid containing 3 μM Linerixibat, 2 μM GF120918A, 25 mM glucose, and 250 μM Lucifer Yellow CH. Next, the transport buffer is removed from the basolateral chambers and replaced with transport buffer containing 1% (w/v) human serum albumin and 2 μM GF120918A. After 60 min incubation at 37 °C, samples are collected from the apical (donor) and basolateral (receiver) compartments and added to acetonitrile (1:1 and 1:2 (v/v), respectively). Receiver samples are then centrifuged and the supernatants are removed and analyzed by LC-MS/MS.

Linerixibat (twice daily; for 14 days) treatment lowers glucose in an animal model of type 2 diabetes.^[3]