| Indication |
Treatment of short bowel syndrome (SBS), malabsorption associated with the removal of the intestine, in adults patients who are dependent on parenteral support. |
| 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. |
| 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 ugohr/mL;
Teduglutide does not accumulate following multiple subcutaneous administrations. |
| Protein binding |
Not Available |
| Biotransformation |
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 |
| 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 |
|