Indications
Teduglutide is prescribed for managing Short Bowel Syndrome (SBS) in both adults and pediatric patients aged one year and older who require parenteral support. This indication highlights its application in providing an alternative therapeutic approach for individuals dependent on parenteral nutrition due to insufficient bowel length to absorb nutrients effectively.
Pharmacodynamics
The pharmacodynamic properties of teduglutide include a significant enhancement in the absorption of gastrointestinal fluids, resulting in an increase of approximately 750-1000 mL/day. Additionally, teduglutide contributes to morphological changes in the intestinal mucosa, evidenced by an increase in both villus height and crypt depth. These changes are associated with improved nutrient absorption. Furthermore, a reduction in fecal weight has been documented, indicating enhanced digestive efficiency. Importantly, teduglutide does not prolong the QTc interval, ensuring cardiovascular safety in its usage.
Absorption
Teduglutide, when administered subcutaneously, follows a one-compartment pharmacokinetic model characterized by first-order absorption in the abdomen, arm, and thigh. The pharmacokinetics of teduglutide are linear with increasing doses. The drug exhibits an absolute bioavailability of 88% via subcutaneous administration, with a time to maximum concentration (Tmax) of 3 to 5 hours. In SBS patients receiving a 0.05 mg/kg dose subcutaneously, the maximum concentration (Cmax) reached is 36 ng/mL, while the area under the curve (AUC) is 0.15 µg·hr/mL. Notably, teduglutide does not accumulate following repeated subcutaneous administrations, supporting a stable therapeutic profile.
Metabolism
Teduglutide's metabolism is anticipated to follow peptide-based drug catabolic pathways, where it is broken down into smaller peptides and amino acids. This metabolic pathway occurs independently of the cytochrome P450 enzyme system, as no formal studies have indicated its involvement. The absence of cytochrome P450 interaction minimizes the risk of drug-drug interactions mediated through this enzyme system.
Mechanism of Action
Teduglutide is a synthetic analogue of the naturally occurring human glucagon-like peptide-2 (GLP-2). GLP-2 is a peptide that is secreted by L-cells in the distal intestine in response to food intake. The biological effects of GLP-2 include enhancement of intestinal and portal blood flow and the inhibition of gastric acid secretion. Teduglutide functions by binding to the glucagon-like peptide-2 receptors found on enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons within the submucosal and myenteric plexus. This binding stimulates the release of several growth factors, including insulin-like growth factor 1 (IGF-1), nitric oxide, and keratinocyte growth factor (KGF). These growth factors are believed to encourage the proliferation of crypt cells and expansion of the gastric mucosal surface area, thereby improving intestinal absorption efficiency.
