Identification

Name
Teduglutide
Accession Number
DB08900
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Other protein based therapies
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 chemical formula
C164H252N44O55S
Protein average weight
3752.0 Da
Sequences
>Protein sequence for teduglutide
HGDGSFSDEMNTILDNLAARDFINWLIQTKITD
Download FASTA Format
Synonyms
  • (Gly2)GLP-2
  • Glucagon-like peptide II (2-glycine) (human)
  • Gly(2)-GLP-2
  • Teduglutide [rDNA origin]
  • Teduglutide Recombinant
External IDs
ALX 0600 / ALX-0600
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GattexKitShire Nps Pharmaceuticals, Inc.2012-12-21Not applicableUs
GattexInjection, powder, lyophilized, for solution5 mg/.5mLSubcutaneousShire Nps Pharmaceuticals, Inc.2012-12-21Not applicableUs
GattexKitShire Nps Pharmaceuticals, Inc.2012-12-21Not applicableUs
RevestiveInjection, powder, for solution5 mgSubcutaneousShire2012-08-30Not applicableEu
RevestiveKit; Powder, for solution5 mgSubcutaneousShire Pharmaceuticals Ireland Limited2015-10-28Not applicableCanada
International/Other Brands
Gattex / Revestive
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
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.

TargetActionsOrganism
AGlucagon-like peptide 2 receptor
agonist
Human
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
DrugInteractionDrug group
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Teduglutide.Approved, Illicit, Investigational
BMS-906024The serum concentration of BMS-906024 can be increased when it is combined with Teduglutide.Investigational
BromazepamThe serum concentration of Bromazepam can be increased when it is combined with Teduglutide.Approved, Illicit
CamazepamThe serum concentration of Camazepam can be increased when it is combined with Teduglutide.Approved, Illicit
CE-326597The serum concentration of CE-326597 can be increased when it is combined with Teduglutide.Investigational
ChlordiazepoxideThe serum concentration of Chlordiazepoxide can be increased when it is combined with Teduglutide.Approved, Illicit
ClobazamThe serum concentration of Clobazam can be increased when it is combined with Teduglutide.Approved, Illicit
ClonazepamThe serum concentration of Clonazepam can be increased when it is combined with Teduglutide.Approved, Illicit
ClorazepateThe serum concentration of Clorazepate can be increased when it is combined with Teduglutide.Approved, Illicit
DelorazepamThe serum concentration of Delorazepam can be increased when it is combined with Teduglutide.Approved, Illicit, Investigational
DiazepamThe serum concentration of Diazepam can be increased when it is combined with Teduglutide.Approved, Illicit, Vet Approved
DoxefazepamThe serum concentration of Doxefazepam can be increased when it is combined with Teduglutide.Experimental
EstazolamThe serum concentration of Estazolam can be increased when it is combined with Teduglutide.Approved, Illicit
EtizolamThe serum concentration of Etizolam can be increased when it is combined with Teduglutide.Approved
FludiazepamThe serum concentration of Fludiazepam can be increased when it is combined with Teduglutide.Approved, Illicit
FlumazenilThe serum concentration of Flumazenil can be increased when it is combined with Teduglutide.Approved
FlunitrazepamThe serum concentration of Flunitrazepam can be increased when it is combined with Teduglutide.Approved, Illicit
FlurazepamThe serum concentration of Flurazepam can be increased when it is combined with Teduglutide.Approved, Illicit
LorazepamThe serum concentration of Lorazepam can be increased when it is combined with Teduglutide.Approved
LormetazepamThe serum concentration of Lormetazepam can be increased when it is combined with Teduglutide.Approved
MedazepamThe serum concentration of Medazepam can be increased when it is combined with Teduglutide.Experimental
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Teduglutide.Approved, Illicit
NetazepideThe serum concentration of Netazepide can be increased when it is combined with Teduglutide.Investigational
NitrazepamThe serum concentration of Nitrazepam can be increased when it is combined with Teduglutide.Approved
OxazepamThe serum concentration of Oxazepam can be increased when it is combined with Teduglutide.Approved
PF-477736The serum concentration of PF-477736 can be increased when it is combined with Teduglutide.Investigational
PirenzepineThe serum concentration of Pirenzepine can be increased when it is combined with Teduglutide.Approved
PrazepamThe serum concentration of Prazepam can be increased when it is combined with Teduglutide.Approved, Illicit
QuazepamThe serum concentration of Quazepam can be increased when it is combined with Teduglutide.Approved, Illicit
SJG-136The serum concentration of SJG-136 can be increased when it is combined with Teduglutide.Investigational
TemazepamThe serum concentration of Temazepam can be increased when it is combined with Teduglutide.Approved
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Teduglutide.Approved
Food Interactions
Not Available

References

General References
  1. 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]
  2. 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]
  3. 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
KEGG Drug
D06053
KEGG Compound
C16049
PubChem Substance
347910383
ChEBI
72305
ChEMBL
CHEMBL2104987
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Teduglutide
ATC Codes
A16AX08 — Teduglutide
AHFS Codes
  • 56:92.00 — Miscellaneous GI Drugs
FDA label
Download (410 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailableHepatic Impairment1
1CompletedNot AvailableImpaired Renal Function1
1CompletedNot AvailablePharmacokinetics and Safety of Elevated Doses1
1CompletedTreatmentHealthy Volunteers1
1Not Yet RecruitingTreatmentPostoperative Fistula1
2CompletedTreatmentCrohn's Disease (CD)2
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
3Active Not RecruitingTreatmentShort Bowel Syndrome (SBS)1
3CompletedTreatmentShort Bowel Syndrome (SBS)7
3RecruitingTreatmentShort Bowel Syndrome (SBS)4
4CompletedTreatmentShort Bowel Syndrome (SBS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionSubcutaneous5 mg/.5mL
Kit
Injection, powder, for solutionSubcutaneous5 mg
Kit; powder, for solutionSubcutaneous5 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5789379No1996-04-142016-04-14Us
US7056886No2002-09-182022-09-18Us
US7847061No2005-11-012025-11-01Us
US9060992No2005-11-012025-11-01Us
US9555079No2005-11-012025-11-01Us
US9545434No2005-11-012025-11-01Us
US9539310No2005-11-012025-11-01Us
US9545435No2005-11-012025-11-01Us
US9592273No2005-11-012025-11-01Us
US9592274No2005-11-012025-11-01Us
US9572867No2005-11-012025-11-01Us

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

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
  1. 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 January 14, 2018 10:04