Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation.

Busby RW, Kessler MM, Bartolini WP, Bryant AP, Hannig G, Higgins CS, Solinga RM, Tobin JV, Wakefield JD, Kurtz CB, Currie MG

The Journal of pharmacology and experimental therapeutics22 Oct 2012Cited by 113 (Europe PMC)

PMID23090647DOI10.1124/jpet.112.199430PepBankPUB-23090647

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study7

4 results from studies that gave the peptide. 2 results from people.

01HumanNon-randomized trialPharmacokinetics
In humans, systemic exposure after oral linaclotide was low.
In plain wordsIn people, little oral linaclotide entered the blood.
Peptide
Linaclotide
Outcome
Not applicableSystemic exposure
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
Systemic exposure to these active peptides is low in rats and humans, and the low systemic and portal vein concentrations of linaclotide and MM-419447 observed in the rat confirmed both peptides are minimally absorbed after oral administration.
Report a problemFND-2309064702
02HumanNon-randomized trialPharmacokinetics
In humans, mean active peptide fecal recovery after oral linaclotide was 3-5%, predominantly MM-419447.
In plain wordsIn people, mean active peptide recovery in feces after oral linaclotide was 3-5%, mainly its metabolite.
Peptide
Linaclotide
Outcome
Not applicableActive peptide fecal recovery
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · oralAs given in this study (human).
Measurements
Active peptide fecal recovery
3 to 5%
human
Source sentences
Summary
After oral administration of linaclotide, <1% of the dose was excreted as active peptide in rat feces and a mean of 3-5% in human feces; in both cases MM-419447 was the predominant peptide recovered.
Report a problemFND-2309064707
03AnimalAnimal study (in vivo)Pharmacokinetics
In rats, oral linaclotide produced low systemic and portal concentrations, indicating minimal absorption.
In plain wordsIn rats, little oral linaclotide entered systemic or portal blood.
Peptide
Linaclotide
Outcome
Not applicableSystemic and portal exposure
Study
ratn: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · oralAs given in this study (rat).
Source sentences
Summary
Systemic exposure to these active peptides is low in rats and humans, and the low systemic and portal vein concentrations of linaclotide and MM-419447 observed in the rat confirmed both peptides are minimally absorbed after oral administration.
Report a problemFND-2309064701
04AnimalAnimal study (in vivo)Pharmacokinetics
In rats, less than 1% of oral linaclotide dose appeared as active peptide in feces, predominantly MM-419447.
In plain wordsIn rats, less than 1% of oral linaclotide appeared as active peptide in feces, mainly its metabolite.
Peptide
Linaclotide
Outcome
Not applicableActive peptide fecal recovery
Study
ratn: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated · oralAs given in this study (rat).
Measurements
Active peptide fecal recovery
< 1%
rat
Source sentences
Summary
After oral administration of linaclotide, <1% of the dose was excreted as active peptide in rat feces and a mean of 3-5% in human feces; in both cases MM-419447 was the predominant peptide recovered.
Report a problemFND-2309064706

Studies that did not test the peptide alone3

In this study, Linaclotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Linaclotide.

05LabNot a test of Linaclotide aloneIn vitro (cell-free)Pharmacokinetics
In laboratory gastrointestinal conditions, linaclotide remained stable in the acidic stomach environment.
In plain wordsIn lab tests, linaclotide remained stable in acidic stomach conditions.
Peptide
Linaclotide
Outcome
Not applicableGastric stability
Study
n: not reported in source
Conditions mimicking the gastrointestinal tract
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Linaclotide is stable in the acidic environment of the stomach and is converted to MM-419447 in the small intestine.
1 context sentence(design, population, supporting numbers)
Summary · context
We examined the metabolic stability of linaclotide in conditions that mimic the gastrointestinal tract and characterized the metabolite MM-419447 (CCEYCCNPACTGC), which contributes to the pharmacologic effects of linaclotide.
In this study, Linaclotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Linaclotide.
Report a problemFND-2309064703
06LabNot a test of Linaclotide aloneIn vitro (cell-free)Pharmacokinetics
In laboratory gastrointestinal conditions, linaclotide converted to MM-419447 in the small intestine.
In plain wordsIn lab tests, linaclotide changed into MM-419447 in small-intestine conditions.
Peptide
Linaclotide
Outcome
Not applicableMetabolite formation
Study
n: not reported in source
Conditions mimicking the gastrointestinal tract
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Linaclotide is stable in the acidic environment of the stomach and is converted to MM-419447 in the small intestine.
1 context sentence(design, population, supporting numbers)
Summary · context
We examined the metabolic stability of linaclotide in conditions that mimic the gastrointestinal tract and characterized the metabolite MM-419447 (CCEYCCNPACTGC), which contributes to the pharmacologic effects of linaclotide.
In this study, Linaclotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Linaclotide.
Report a problemFND-2309064704
07LabNot a test of Linaclotide aloneIn vitro (cell-free)Pharmacokinetics
In laboratory gastrointestinal conditions, linaclotide underwent disulfide reduction followed by proteolysis and degradation in the small intestine.
In plain wordsIn lab tests, linaclotide disulfide bonds broke before the peptide degraded in small-intestine conditions.
Peptide
Linaclotide
Outcome
Not applicableIntestinal degradation
Study
n: not reported in source
Conditions mimicking the gastrointestinal tract
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
The disulfide bonds of both peptides are reduced in the small intestine, where they are subsequently proteolyzed and degraded.
1 context sentence(design, population, supporting numbers)
Summary · context
We examined the metabolic stability of linaclotide in conditions that mimic the gastrointestinal tract and characterized the metabolite MM-419447 (CCEYCCNPACTGC), which contributes to the pharmacologic effects of linaclotide.
In this study, Linaclotide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Linaclotide.
Report a problemFND-2309064705

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 ongoing · source ClinicalTrials.gov (opens in a new tab)

RecruitingEarly phase 1NCT07569419

Proof of Principle Study for an Efficacy Trial of Linaclotide for Cystic Fibrosis

University of Nottinghamn = 269 Mar 2026 to est. Oct 2026

Cystic Fibrosis (CF)

Trial page ClinicalTrials.govUpdated 6 May 2026

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
28 Oct 2026, 02:03 UTC
Study results updated
Version 1
27 Oct 2026, 16:34 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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