1 ent with the FDA-approved oral GUCY2C ligand
linaclotide.
2 with chemically induced VP but refractory to
linaclotide.
3 tive signaling and VP that was refractory to
linaclotide.
4 clic guanosine-3',5'-monophosphate (cGMP) by
linaclotide.
5 irty-one patients with SSc were treated with
linaclotide.
6 , respectively) but no significant effect of
linaclotide 100-microg dose.
7 ntrolled study evaluated the effects of oral
linaclotide,
100 and 1000 microg once daily, in 36 women
8 pation-predominant irritable bowel syndrome,
linaclotide 1000 microg once daily significantly acceler
9 (P = ns), with a significant acceleration by
linaclotide 1000 microg vs placebo (P = .004 and P = .01
10 Low-dose
linaclotide (
145 mcg daily) was used in 18 patients and
11 Patients received either placebo or
linaclotide,
145 mug or 290 mug, once daily for 12 weeks
12 ks (0.74, 0.66-0.83, P-score 0.79), although
linaclotide 290 mug once daily and prucalopride 2 mg onc
13 ents in gastrointestinal half-lives (>8 h vs
linaclotide 48 min), and most remained active at low nan
14 to the preponderance of evidence we focus on
linaclotide,
a 14-amino acid GC-C agonist with very low
15 Linaclotide,
a minimally absorbed, 14-amino acid peptide
16 Oral
linaclotide,
a novel agonist of guanylate cylase-C, stim
17 Linaclotide,
a peripherally restricted 14 aa peptide app
18 We report our experience with
linaclotide,
a selective agonist of guanylate cyclase C
19 Linaclotide,
across a wide range of doses, significantly
20 During 26 weeks of
linaclotide administration, a significantly greater perc
21 hese results suggest that GC-C agonists like
linaclotide alleviate colorectal pain and hypersensitivi
22 ST and its structural analog,
linaclotide,
an FDA-approved oral secretagog, induced fl
23 erefore designed and synthesized a series of
linaclotide analogues employing a variety of strategic m
24 , cGMP, was released after administration of
linaclotide and also inhibited nociceptors.
25 6.0% of the patients who received 145 mug of
linaclotide and by 19.4% and 21.3% of the patients who r
26 aled distinct safety profiles: lubiprostone,
linaclotide,
and elobixibat were linked to the highest r
27 overall efficacy and safety of lubiprostone,
linaclotide,
and elobixibat.
28 disulfide reduction/multidesulfurization of
linaclotide,
aprotinin, and wheat protein.
29 ed controlled trials of clinical efficacy of
linaclotide are warranted.
30 1.3% of the patients who received 290 mug of
linaclotide,
as compared with 3.3% and 6.0% of those who
31 We assessed the efficacy and safety of
linaclotide at a daily dose range of 75-600 mug in IBS-C
32 study of 420 patients with IBS-C given oral
linaclotide at doses of 75, 150, 300, or 600 mug or plac
33 or = .05 for each pair-wise comparison of a
linaclotide dose to placebo).
34 sessed the safety and efficacy of a range of
linaclotide doses in patients with chronic constipation.
35 rom baseline were 2.6, 3.3, 3.6, and 4.3 for
linaclotide doses of 75, 150, 300, and 600 microg, respe
36 line were -0.71, -0.71, -0.90, and -0.86 for
linaclotide doses of 75, 150, 300, and 600 mug, respecti
37 Conversely, the GUCY2C agonist
linaclotide eliminated neuronal hyperexcitability produc
38 ma Center and identified patients prescribed
linaclotide for refractory lower GI manifestations.
39 nd points were significantly greater in both
linaclotide groups than in the placebo groups.
40 ion of treatment in 4.2% of patients in both
linaclotide groups.
41 verse events was similar between placebo and
linaclotide groups.
42 The panel made a strong recommendation for
linaclotide (
high certainty) and conditional recommendat
43 All doses of
linaclotide improved the weekly rate of SBM (primary end
44 he potential long-term risks and benefits of
linaclotide in chronic constipation.
45 imed to determine the efficacy and safety of
linaclotide in patients with chronic constipation.
46 In mice,
linaclotide inhibited colonic nociceptors with greater e
47 At the time of
linaclotide initiation, 23 of these patients (74%) were
48 Linaclotide is a minimally absorbed agonist of guanylate
49 Linaclotide is a minimally absorbed peptide agonist of t
50 Linaclotide is a minimally absorbed peptide agonist of t
51 Linaclotide is a novel therapeutic agent, which is a gua
52 Linaclotide is a well-tolerated and efficacious pro-secr
53 We found that low-dose
linaclotide is an effective option and may be better tol
54 Linaclotide is an orally administered peptide drug for t
55 Clinical trials have demonstrated that
linaclotide is effective, safe and well tolerated in pat
56 Linaclotide is however degraded in the intestinal enviro
57 We have identified an analgesic mechanism of
linaclotide:
it activates GC-C expressed on mucosal epit
58 (osmotic or stimulant laxatives, elobixibat,
linaclotide,
lubiprostone, mizagliflozin, naronapride, p
59 Basal and
linaclotide-
mediated small intestinal transit was higher
60 We determined the effects of
linaclotide on colonic sensory afferents in healthy mice
61 d to groups given an oral placebo or 290 mug
linaclotide once daily for 26 weeks.
62 roups given 75, 150, 300, or 600 microg oral
linaclotide or placebo once daily for 4 weeks.
63 Intra-colonic administration of
linaclotide reduced signaling of noxious colorectal dist
64 Little is known about the mechanism by which
linaclotide reduces abdominal pain in patients with IBS-
65 We also found that
linaclotide reduces chronic abdominal pain in patients w
66 Linaclotide responders were on medication for at least 1
67 rticle highlights the mechanism of action of
linaclotide,
reviews published literature based on a sea
68 ucosa, but not neurons, was found to express
linaclotide'
s target, GC-C.
69 All doses of
linaclotide significantly improved bowel habits, includi
70 Likewise, most doses of
linaclotide significantly improved other abdominal sympt
71 Likewise,
linaclotide significantly improved the weekly rate of co
72 In these two 12-week trials,
linaclotide significantly reduced bowel and abdominal sy
73 he following agents: tenapanor, plecanatide,
linaclotide,
tegaserod, lubiprostone, polyethylene glyco
74 Linaclotide therapy was associated with few adverse even
75 In healthy volunteers,
linaclotide was safe, well tolerated, increased stool fr
76 The effects of
linaclotide were lost in Gucy2c(-/-) mice and prevented
77 eived placebo (P<0.01 for all comparisons of
linaclotide with placebo).