TABLE 3

Chloride binding by veverimer in matrices mimicking the GI tract

MatrixIncubation Time (h)Anion Bound (mmol/g Polymer)
ChloridePhosphateCitrateTaurocholate
SGFa1610.7 ± 0.4N/AN/AN/A
SIBb14.3 ± 0.11.5 ± 0.3N/AN/A
SOBc243.8 ± 0.30.1 ± 0.1d<0.1e<0.1e
  • N/A, not applicable.

  • a SGF, pH = 1.2; it mimics the acidic environment of the fasted stomach and reflects an optimal condition for binding of HCl.

  • b SIB, pH = 5.5; pH is representative of the human proximal small intestine (duodenum and early jejunum), and that contains chloride and a high conc. of phosphate as a potential competing anion to chloride. The solution was buffered by 2-(N-morpholino)ethanesulfonic acid.

  • c SOB, pH = 6.2; pH and competing anion content (bile acid, phosphate, citrate, oleic acid, and acetate) represent components of the human distal small intestine (late jejunum, ileum) and cecum. The solution was buffered by N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid.

  • d Phosphate conc. used to calculate phosphate binding capacity of veverimer lots were estimated by calculating the change in the phosphate peak area before and after incubating the polymer in SOB.

  • e Citrate and taurocholate peaks for veverimer lots were not well separated in the IC chromatogram because of method limitations. Combined peak area was used to estimate conc. of these anions before and after incubating the polymer in SOB. Oleic acid was not determined because it was not detected by the IC method used.