Teduglutide - DrugBank

ID Pharmacology Interactions References Trials Economics Properties Taxonomy

Targets (1)

Identification

Name

Teduglutide

Accession Number

DB08900

Type

Biotech

Groups

Approved

Description

Teduglutide is a glucagon-like peptide-2 (GLP-2) analogue. It is made up of 33 amino acids and is manufactured using a strain of Escherichia coli modified by recombinant DNA technology. Teduglutide differs from GLP-2 by one amino acid (alanine is substituted by glycine). The significance of this substitution is that teduglutide is longer acting than endogenous GLP-2 as it is more resistant to proteolysis from dipeptidyl peptidase-4. FDA approved on December 21, 2012.

Protein structure

Protein chemical formula

C₁₆₄H₂₅₂N₄₄O₅₅S

Protein average weight

3752.0 Da

Sequences

>Protein sequence for teduglutide
HGDGSFSDEMNTILDNLAARDFINWLIQTKITD

Download FASTA Format

Synonyms

(Gly2)glp-2

ALX 0600

ALX-0600

Gattex

Glucagon-like peptide ii (2-glycine) (human)

Gly(2)-glp-2

HGDGSFSDEMNTILDNLAARDFINWLIQTKITD

His-gly-asp-gly-ser-phe-ser-asp-glu-met-asn-thr-ile-leu-asp-asn-leu-ala-ala-arg-asp-phe-ile-asn-trp-leu-ile-gln-thr-lys-ile-thr-asp

Teduglutide [rDNA origin]

Teduglutide Recombinant

External IDs

Not Available

Product Ingredients

Not Available

Approved Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Gattex	Kit			Shire Nps Pharmaceuticals, Inc.	2012-12-21	Not applicable	US
Gattex	Injection, powder, lyophilized, for solution	5 mg/.5mL	Subcutaneous	Shire Nps Pharmaceuticals, Inc.	2012-12-21	Not applicable	US
Gattex	Kit			Shire Nps Pharmaceuticals, Inc.	2012-12-21	Not applicable	US
Revestive	Injection, powder, for solution	5 mg	Subcutaneous	Shire	2012-08-30	Not applicable	EU
Revestive	Kit; Powder, for solution	5 mg	Subcutaneous	Shire Pharmaceuticals Ireland Limited	2015-10-28	Not applicable	Canada

Approved Generic Prescription Products

Not Available

Approved Over the Counter Products

Not Available

Unapproved/Other Products

Not Available

International Brands

Name	Company
Revestive	Not Available

Brand mixtures

Not Available

Categories

UNII

7M19191IKG

CAS number

197922-42-2

Pharmacology

Indication

Treatment of short bowel syndrome (SBS), malabsorption associated with the removal of the intestine, in adults patients who are dependent on parenteral support.

Structured Indications

Short Bowel Syndrome (SBS)

Pharmacodynamics

An enhancement of gastrointestinal fluid absorption (750-1000 mL/day) was observed following daily administrations of teduglutide. An increase in villus height and crypt depth of the intestinal mucosa was also noted. A decrease in fecal weight has also been observed. Teduglutide does not prolong the QTc interval.

Mechanism of action

Teduglutide is an analog of naturally occurring human glucagon-like peptide-2 (GLP-2), a peptide secreted by L-cells of the distal intestine in response to meals. GLP-2 increases intestinal and portal blood flow and inhibit gastric acid secretion. Teduglutide binds to the glucagon-like peptide-2 receptors located in enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus. This causes the release of insulin-like growth factor (IGF)-1, nitric oxide and keratinocyte growth factor (KGF). These growth factors may contribute to the increase in crypt cell growth and surface area of the gastric mucosa. Ultimately, absorption through the intestine is enhanced.

Target	Kind	Pharmacological action	Actions	Organism	UniProt ID
Glucagon-like peptide 2 receptor	Protein	yes	agonist	Human	O95838	details

Absorption

The pharmacokinetic profile of teduglutide (when administered subcutaneously) is described by a one-compartment model with first order absorption in the abdomen, arm, and thigh. With escalating doses, teduglutide demonstrates linear pharmacokinetics. Absolute bioavailability, SubQ = 88%; Tmax, SubQ = 3-5 hours;
Cmax, 0.05 mg/kg SubQ, SBS patients = 36 ng/mL; AUC, 0.05 mg/kg SubQ, SBS patients = 0.15 µg•hr/mL; Teduglutide does not accumulate following multiple subcutaneous administrations.

Volume of distribution

Vd, healthy subjects = 103 mL/kg

Protein binding

Not Available

Metabolism

Although a formal investigation has not been conducted, it is expected because teduglutide is a peptide-based drug, it will be degraded into smaller peptides and amino acids via catabolic pathways. The cytochrome P450 enzyme system is not involved in the metabolism of this drug.

Route of elimination

Urine

Half life

Terminal half-life, healthy subjects = 2 hours; Terminal half-life, SBS patients = 1.3 hours

Clearance

Plasma clearance, healthy subjects = 123 mL/hr/kg; This value indicates that teduglutide is primarily cleared by the kidney.

Toxicity

The most common adverse reactions (≥ 10%) across all studies with GATTEX are abdominal pain, injection site reactions, nausea, headaches, abdominal distension, upper respiratory tract infection. In addition, vomiting and fluid overload were reported in the SBS studies (1 and 3) at rates ≥ 10%.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction	Drug group
Alprazolam	The serum concentration of Alprazolam can be increased when it is combined with Teduglutide.	Approved, Illicit, Investigational
Bromazepam	The serum concentration of Bromazepam can be increased when it is combined with Teduglutide.	Approved, Illicit
Camazepam	The serum concentration of Camazepam can be increased when it is combined with Teduglutide.	Approved, Illicit
Chlordiazepoxide	The serum concentration of Chlordiazepoxide can be increased when it is combined with Teduglutide.	Approved, Illicit
Clonazepam	The serum concentration of Clonazepam can be increased when it is combined with Teduglutide.	Approved, Illicit
Clorazepate	The serum concentration of Clorazepate can be increased when it is combined with Teduglutide.	Approved, Illicit
Delorazepam	The serum concentration of Delorazepam can be increased when it is combined with Teduglutide.	Approved, Illicit
Diazepam	The serum concentration of Diazepam can be increased when it is combined with Teduglutide.	Approved, Illicit, Vet Approved
Estazolam	The serum concentration of Estazolam can be increased when it is combined with Teduglutide.	Approved, Illicit
Etizolam	The serum concentration of Etizolam can be increased when it is combined with Teduglutide.	Approved
Fludiazepam	The serum concentration of Fludiazepam can be increased when it is combined with Teduglutide.	Approved, Illicit
Flumazenil	The serum concentration of Flumazenil can be increased when it is combined with Teduglutide.	Approved
Flunitrazepam	The serum concentration of Flunitrazepam can be increased when it is combined with Teduglutide.	Approved, Illicit
Flurazepam	The serum concentration of Flurazepam can be increased when it is combined with Teduglutide.	Approved, Illicit
Lorazepam	The serum concentration of Lorazepam can be increased when it is combined with Teduglutide.	Approved
Midazolam	The serum concentration of Midazolam can be increased when it is combined with Teduglutide.	Approved, Illicit
Netazepide	The serum concentration of Netazepide can be increased when it is combined with Teduglutide.	Investigational
Nitrazepam	The serum concentration of Nitrazepam can be increased when it is combined with Teduglutide.	Approved
Oxazepam	The serum concentration of Oxazepam can be increased when it is combined with Teduglutide.	Approved
PF-477736	The serum concentration of Pf 00477736 can be increased when it is combined with Teduglutide.	Investigational
Pirenzepine	The serum concentration of Pirenzepine can be increased when it is combined with Teduglutide.	Approved
Prazepam	The serum concentration of Prazepam can be increased when it is combined with Teduglutide.	Approved, Illicit
Temazepam	The serum concentration of Temazepam can be increased when it is combined with Teduglutide.	Approved
Triazolam	The serum concentration of Triazolam can be increased when it is combined with Teduglutide.	Approved

Food Interactions

Not Available

References

Synthesis Reference

Not Available

General References

Burness CB, McCormack PL: Teduglutide: a review of its use in the treatment of patients with short bowel syndrome. Drugs. 2013 Jun;73(9):935-47. doi: 10.1007/s40265-013-0070-y. [PubMed:23729002 ]
Semrad CE: The long road to a new short-bowel therapy: teduglutide for clinical use. Clin Gastroenterol Hepatol. 2013 Jul;11(7):824-5. doi: 10.1016/j.cgh.2013.03.030. Epub 2013 Apr 13. [PubMed:23591284 ]
Jeppesen PB: Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome. Therap Adv Gastroenterol. 2012 May;5(3):159-71. doi: 10.1177/1756283X11436318. [PubMed:22570676 ]

External Links

Resource	Link
Drug Product Database	22636
RxList	http://www.rxlist.com/gattex-drug.htm
Drugs.com	http://www.drugs.com/mtm/teduglutide.html
Wikipedia	Teduglutide

ATC Codes

A16AX08 — Teduglutide

AHFS Codes

56:92

PDB Entries

Not Available

FDA label

Download (410 KB)

MSDS

Not Available

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Healthy Volunteers	1
1	Completed	Not Available	Hepatic Impairment	1
1	Completed	Not Available	Impaired Renal Function	1
1	Completed	Not Available	Pharmacokinetics and Safety of Elevated Doses	1
1	Completed	Treatment	Healthy Volunteers	1
1	Not Yet Recruiting	Treatment	Postoperative Fistula	1
2	Completed	Treatment	Crohn's Disease (CD)	2
2	Recruiting	Treatment	HIV Disease	1
3	Active Not Recruiting	Treatment	Short Bowel Syndrome (SBS)	2
3	Completed	Treatment	Short Bowel Syndrome (SBS)	6
3	Recruiting	Treatment	Short Bowel Syndrome (SBS)	3
4	Completed	Treatment	Short Bowel Syndrome (SBS)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Injection, powder, lyophilized, for solution	Subcutaneous	5 mg/.5mL
Kit
Injection, powder, for solution	Subcutaneous	5 mg
Kit; powder, for solution	Subcutaneous	5 mg

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US5789379	No	1996-04-14	2016-04-14	US
US7056886	No	2002-09-18	2022-09-18	US
US7847061	No	2005-11-01	2025-11-01	US
US9060992	No	2005-11-01	2025-11-01	US

Properties

State

Liquid

Experimental Properties

Not Available

Taxonomy

Description

Not Available

Kingdom

Organic Compounds

Super Class

Organic Acids

Class

Carboxylic Acids and Derivatives

Sub Class

Amino Acids, Peptides, and Analogues

Direct Parent

Peptides

Alternative Parents

Not Available

Substituents

Not Available

Molecular Framework

Not Available

External Descriptors

Not Available

Targets

Details

1. Glucagon-like peptide 2 receptor

Kind: Protein
Organism: Human
Pharmacological action: yes
Actions: agonist

General Function:: Glucagon receptor activity
Specific Function:: This is a receptor for glucagon-like peptide 2. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:: GLP2R
Uniprot ID:: O95838
Uniprot Name:: Glucagon-like peptide 2 receptor
Molecular Weight:: 63000.84 Da

References

Burness CB, McCormack PL: Teduglutide: a review of its use in the treatment of patients with short bowel syndrome. Drugs. 2013 Jun;73(9):935-47. doi: 10.1007/s40265-013-0070-y. [PubMed:23729002 ]

Drug created on June 05, 2013 23:11 / Updated on July 25, 2017 12:02

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Targets

References