Dasiglucagon API Manufacturers

General Description:

Dasiglucagon, identified by CAS number 1544300-84-6, is a notable compound with significant therapeutic applications. Dasiglucagon is a glucagon analog that acts to increase blood sugar levels. It consists of 29 amino acids similar to endogenous glucagon; however, it contains seven substituted amino acids for improved physical and chemical stability in its drug formulation. In March 2021, the FDA approved dasiglucagon to treat severe hypoglycemia in patients six years and older with diabetes. It is available as a subcutaneous injection marketed as ZEGALOGUE. Severe hypoglycemia is an acute, life-threatening medical condition resulting from a profound drop in blood glucose levels. It is characterized by neurological impairment, with manifestations like loss of consciousness and seizure. Hypoglycemia is a common side effect of antidiabetic treatments, most notably insulin and sulfonylureas. Although it tends to be more common in type 1 diabetes mellitus, occurring in about 22% to 46% of patients annually, about 7% to 25% of patients with type 2 diabetes mellitus treated with insulin experience severe hypoglycemia a year. Even with close monitoring of blood glucose levels, it is not always possible to prevent severe hypoglycemic events in patients with diabetes, and children are particularly at risk for experiencing severe hypoglycemia. Treatments for severe hypoglycemia have mostly been limited to intravenous dextrose and different glucagon formulations. The approval of dasiglucagon marks the first glucagon analog approved for severe hypoglycemia treatment that does not require administration by a healthcare professional.

Indications:

This drug is primarily indicated for: Dasiglucagon is an antihypoglycemic agent indicated for the treatment of severe hypoglycemia in pediatric and adult patients with diabetes aged 6 years and above. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Dasiglucagon undergoes metabolic processing primarily in: Like endogenous glucagon, dasiglucagon undergoes proteolytic degradation pathways in blood, liver, and kidney. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Dasiglucagon are crucial for its therapeutic efficacy: Following subcutaneous administration of 0.6 mg dasiglucagon, the mean peak plasma concentration was 5110 pg/mL (1510 pmol/L). T_max was 35 minutes. In pediatric patients with type 1 diabetes, the mean peak plasma concentration of 3920 pg/mL occurred at around 21 minutes. Dasiglucagon has a higher absorption rate than traditional reconstituted glucagon. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Dasiglucagon is an important consideration for its dosing schedule: The half-life was approximately 30 minutes following subcutaneous administration. Dasiglucagon has a longer plasma elimination half-life than traditional reconstituted glucagon. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Dasiglucagon is distributed throughout the body with a volume of distribution of: The mean apparent volume of distribution ranged from 47 L to 57 L after subcutaneous administration. This metric indicates how extensively the drug permeates into body tissues.

Pharmacodynamics:

Dasiglucagon exerts its therapeutic effects through: Dasiglucagon works to increase blood glucose levels under normal and hypoglycemic conditions. After administration of dasiglucagon in adult patients with type 1 diabetes, the mean glucose increase from baseline at 90 minutes was 168 mg/dL. In pediatric patients with type 1 diabetes aged seven to 17 years, the mean glucose increase at 60 minutes after administration of dasiglucagon was 162 mg/dL. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Dasiglucagon functions by: Dasiglucagon is an analog of glucagon, which is a peptide hormone responsible for increasing blood glucose levels. It has the same mechanism of action as endogenous glucagon by acting as an agonist at glucagon receptors, which are G-coupled receptors expressed throughout the body. Dasiglucagon binds to glucagon receptors in the liver, which activates Gsα and Gq, and consequently, adenylate cyclase. Adenyl cyclase increases intracellular cyclic AMP, which stimulates glycogenolysis and glucogenesis in the liver. As glucose is primarily released from liver glycogen stores, hepatic stores of glycogen are crucial for dasiglucagon to exert its antihypoglycemic effects. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Dasiglucagon belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Dasiglucagon is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Antihypertensive Agents, Antihypoglycemic Agent, Glucagon Receptor Agonists, Hormones, Hormones, Hormone Substitutes, and Hormone Antagonists, Increased Glycogenolysis, Pancreatic Hormones, Peptide Hormones, Peptides, Proglucagon. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Dasiglucagon include:

• Molecular Weight: 3382.0
• Molecular Formula: C152H222N38O50