1 ent with the FDA-approved oral GUCY2C ligand
linaclotide.
2 clic guanosine-3',5'-monophosphate (cGMP) by
linaclotide.
3 , respectively) but no significant effect of
linaclotide 100-microg dose.
4 ntrolled study evaluated the effects of oral
linaclotide,
100 and 1000 microg once daily, in 36 women
5 pation-predominant irritable bowel syndrome,
linaclotide 1000 microg once daily significantly acceler
6 (P = ns), with a significant acceleration by
linaclotide 1000 microg vs placebo (P = .004 and P = .01
7 Patients received either placebo or
linaclotide,
145 mug or 290 mug, once daily for 12 weeks
8 Linaclotide,
a minimally absorbed, 14-amino acid peptide
9 Oral
linaclotide,
a novel agonist of guanylate cylase-C, stim
10 Linaclotide,
a peripherally restricted 14 aa peptide app
11 Linaclotide,
across a wide range of doses, significantly
12 During 26 weeks of
linaclotide administration, a significantly greater perc
13 hese results suggest that GC-C agonists like
linaclotide alleviate colorectal pain and hypersensitivi
14 ST and its structural analog,
linaclotide,
an FDA-approved oral secretagog, induced fl
15 , cGMP, was released after administration of
linaclotide and also inhibited nociceptors.
16 6.0% of the patients who received 145 mug of
linaclotide and by 19.4% and 21.3% of the patients who r
17 ed controlled trials of clinical efficacy of
linaclotide are warranted.
18 1.3% of the patients who received 290 mug of
linaclotide,
as compared with 3.3% and 6.0% of those who
19 We assessed the efficacy and safety of
linaclotide at a daily dose range of 75-600 mug in IBS-C
20 study of 420 patients with IBS-C given oral
linaclotide at doses of 75, 150, 300, or 600 mug or plac
21 or = .05 for each pair-wise comparison of a
linaclotide dose to placebo).
22 sessed the safety and efficacy of a range of
linaclotide doses in patients with chronic constipation.
23 rom baseline were 2.6, 3.3, 3.6, and 4.3 for
linaclotide doses of 75, 150, 300, and 600 microg, respe
24 line were -0.71, -0.71, -0.90, and -0.86 for
linaclotide doses of 75, 150, 300, and 600 mug, respecti
25 nd points were significantly greater in both
linaclotide groups than in the placebo groups.
26 ion of treatment in 4.2% of patients in both
linaclotide groups.
27 verse events was similar between placebo and
linaclotide groups.
28 All doses of
linaclotide improved the weekly rate of SBM (primary end
29 he potential long-term risks and benefits of
linaclotide in chronic constipation.
30 imed to determine the efficacy and safety of
linaclotide in patients with chronic constipation.
31 In mice,
linaclotide inhibited colonic nociceptors with greater e
32 Linaclotide is a minimally absorbed agonist of guanylate
33 Linaclotide is a minimally absorbed peptide agonist of t
34 Linaclotide is a minimally absorbed peptide agonist of t
35 Linaclotide is a novel therapeutic agent, which is a gua
36 Clinical trials have demonstrated that
linaclotide is effective, safe and well tolerated in pat
37 We have identified an analgesic mechanism of
linaclotide:
it activates GC-C expressed on mucosal epit
38 We determined the effects of
linaclotide on colonic sensory afferents in healthy mice
39 d to groups given an oral placebo or 290 mug
linaclotide once daily for 26 weeks.
40 roups given 75, 150, 300, or 600 microg oral
linaclotide or placebo once daily for 4 weeks.
41 Intra-colonic administration of
linaclotide reduced signaling of noxious colorectal dist
42 Little is known about the mechanism by which
linaclotide reduces abdominal pain in patients with IBS-
43 We also found that
linaclotide reduces chronic abdominal pain in patients w
44 rticle highlights the mechanism of action of
linaclotide,
reviews published literature based on a sea
45 ucosa, but not neurons, was found to express
linaclotide'
s target, GC-C.
46 All doses of
linaclotide significantly improved bowel habits, includi
47 Likewise, most doses of
linaclotide significantly improved other abdominal sympt
48 Likewise,
linaclotide significantly improved the weekly rate of co
49 In these two 12-week trials,
linaclotide significantly reduced bowel and abdominal sy
50 Linaclotide therapy was associated with few adverse even
51 In healthy volunteers,
linaclotide was safe, well tolerated, increased stool fr
52 The effects of
linaclotide were lost in Gucy2c(-/-) mice and prevented
53 eived placebo (P<0.01 for all comparisons of
linaclotide with placebo).