Dexloxiglumide

461.38

461.38

69DY40RH9B

DTXSID50152604

95.9

4.40280

1.233±0.06 g/cm3(Predicted)

632.2±55.0 °C(Predicted)

336.1ºC

1.537

20/21/22-36/37/38

26-36-37/39

Xn,Xi

94-98%

For the treatment of Irritable Bowel Syndrome (IBS) and Gastroesophageal Reflux Disease (GERD).

Dexloxiglumide is a selective cholecystokinin type A (CCKA) receptor antagonist. In October 2003, following the completion of two phase III clinical studies involving dexloxiglumide in women with constipation-predominant irritable bowel syndrome (IBS), Forest Laboratories decided to discontinue development of the drug for this indication. The results of the studies showed that dexloxiglumide did not show statistically significant favorability over placebo. Rotta Research is continuing a phase III trial of a different design in Europe for the IBS indication and also for gastroesophogeal reflux disease.

Rapidly and extensively absorbed after single oral administration in humans with an absolute bioavailability of 48%. The incomplete bioavailability is due to both incomplete absorption and hepatic first-pass effect.

Cytochrome P450 (CYP) 3A4/5 and CYP2C9 have been implicated in the metabolism of dexloxiglumide to produce O-demethyl dexloxi-glumide. This metabolite is further oxidised to dexloxiglumide carboxylic acid. These two major metabolites (accounting for up to 50% of dexloxiglumide elimination) have been identified. However, in human plasma the unchanged drug represents the major (up to 91%) component of the metabolic profile. The parent drug is believed to be the major contributor to the efficacy of the compound, since its major metabolites are pharmacologically inactive.|Dexloxiglumide has known human metabolites that include 4-[(3,4-Dichlorobenzoyl)amino]-5-[3-hydroxypropyl(pentyl)amino]-5-oxopentanoic acid.

CCKA antagonists target receptors in the gastrointestinal system to increase gastric emptying and intestinal motility, as well as modulate intestinal sensitivity to distension.

dexloxiglumide