Tu2078 The Effect of Lubiprostone on Regional Alimentary Tract Transit Times Measured by Wireless Motility Capsule in Patients With Chronic Constipation

Abstract

Introduction: Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces a chloride-rich intestinal fluid secretion which diminishes viscoelasticity of luminal contents and increases lubrication. These effects have led to increased stool frequency and relief of symptoms in patients with chronic constipation (CC). While radionuclide studies have indicated acceleration in colon transit, the impact of lubiprostone on transit times in specific regions of the gut has not been clarified. These measurements can now be achieved by the novel wireless motility capsule (WMC) technology in patients with CC. Our aim was to investigate the effects of lubiprostone on gastric emptying (GET), small bowel (SBTT), colon (CTT) and small/large bowel (SLBTT) transit times assessed by WMC in CC (Rome III) patients. Methods: Twenty nine female patients with CC, mean age 38 (19-64) mean weight 167 lbs (111-305) were tested with WMC before treatment and on day number 8 after receiving 24 mcg BID of lubiprostone. GET was calculated from the time WMC was ingested until the point at which there was an abrupt and sustained increase in pH of more than 2 units from the gastric pH to an absolute pH of .6.0. SBTT was defined as the elapsed time from capsule leaving the stomach until capsule arrived at the cecum. This was determined by a sudden drop of pH.1 unit, for longer than 1 h, which was preceded by a gradual, sustained rise in pH as the capsule passes through the distal small bowel. CTT was defined as the time interval between the point of entry into the cecum and the exit of WMC from the body. SLBTT includes SBTT and CTT. Statistical analysis, using Mann-Whitney Rank Sum Test was performed using Sigma-Stat software. Results are presented as Median with 25-75 percentiles range. Results: After administration of lubiprostone gastric emptying was slowed by 14.5% to 4.02h (2.27-8.82) versus 3.51h (2.38-12.83) at baseline (P=0.913); SBTT was significantly accelerated by 12.2% to 4.03h (3.13-4.49) when compared with 4.59 h (4.00-6.32) at baseline (P=0.010) and CTT was accelerated by 10.1% to 35.1h (22.66-47.99) vs 39.05h (22.61-63.39) before treatment ( P=0.328). The comparison of SLBTT before and after therapy with lubiprostone showed 18.9% reduction of this regional transit time with median being 46.24h (30.97-80.47) at baseline and 37.55h (24.49-54.21) while on medication (P=0.128). Conclusions: 1) During treatment with lubiprostone the acceleration of SBTT is more pronounced that colon transit in CC patients. 2) This implies that type 2 chloride channel activation within the small bowel does affect small intestine motility patterns in patients with chronic constipation. 3) The very modest delay in gastric emptying was not accompanied by clinically relevant nausea and is unlikely to explain the nausea side effect profile of lubiprostone.