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| Primary information |
|---|
| ID | 10652 |
| Therapeutic ID | Th1137 |
| Protein Name | Teduglutide |
| Sequence | >Th1137_Teduglutide
HGDGSFSDEMNTILDNLAARDFINWLIQTKITD
|
| Molecular Weight | 3752 |
| Chemical Formula | C164H252N44O55S |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Terminal half-life - 2 hrs. |
| Description | Recombinant (E.coli derived) glucagon-like peptide-2 (GLP-2) analogue, made up of 33 amino acids. It differs from GLP-2 by one amino acid (A to G), which makes it more resistant to dipeptidyl peptidase-4 proteolysis, giving it a longer half-life as compared to endogenous GLP-2. FDA approved on December 21, 2012. |
| Indication/Disease | Treatment of short bowel syndrome (SBS), malabsorption associated with the removal of the intestine, in adults patients who are dependent on parenteral support. |
| 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. |
| 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%. |
| 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. |
| 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. |
| Vd, healthy subjects = 103 mL/kg |
| Clearance | Plasma clearance, healthy subjects = 123 mL/hr/kg; This value indicates that teduglutide is primarily cleared by the kidney. |
| Categories | NA |
| Patents Number | US5789379 |
| Date of Issue | 8-Apr-1998 |
| Date of Expiry | 14-10-2020 |
| Drug Interaction | NA |
| Target | Glucagon-like peptide 2 receptor |
| Brand Name | Gattex |
| Company | NPS Pharmaceuticals, Inc |
| Brand Description | NPS Pharmaceuticals, Inc |
| Prescribed For | Short Bowel Syndrome (SBS) |
| Chemical Name | NA |
| Formulation | Each single-use vial of GATTEX contains 5 mg of teduglutide as a white lyophilized powder for solution for subcutaneous injection. In addition to the active pharmaceutical ingredient (teduglutide), each vial of GATTEX contains 3.88 mg L-histidine, 15 mg mannitol, 0.644 mg monobasic sodium phosphate monohydrate, 3.434 mg dibasic sodium phosphate heptahydrate as excipients. No preservatives are present. |
| Physical Appearance | Teduglutide drug substance is a clear, colorless to light-straw–colored liquid. |
| Route of Administration | Subcutaneous |
| Recommended Dosage | 0.05 mg/kg body weight administered by subcutaneous injection once daily |
| Contraindication | NA |
| Side Effects | abdominal pain , injection site reactions, nausea, headaches , abdominal distension, upper respiratory tract infection. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |