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General Description:

Triheptanoin, identified by CAS number 620-67-7, is a notable compound with significant therapeutic applications. Triheptanoin is a source of heptanoate fatty acids, which can be metabolized without the enzymes of long chain fatty acid oxidation. In clinical trials, patients with long chain fatty acid oxidation disorders (lc-FAODs) treated with triheptanoin are less likely to develop hypoglycemia, cardiomyopathy, rhabdomyolysis, and hepatomegaly. Complications in lc-FAOD patients are reduced from approximately 60% to approximately 10% with the addition of triheptanoin. Triheptanoin was granted FDA approval on 30 June 2020.

Indications:

This drug is primarily indicated for: Triheptanoin is a medium chain triglyceride indicated to provide calories and fatty acids to treat long chain fatty acid oxidation disorders (lc-FAODs). Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Triheptanoin undergoes metabolic processing primarily in: Triheptanoin is hydrolysed to heptanoate, which can be further metabolized to β-hydroxypentanoate or β-hydroxybutyrate. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Triheptanoin are crucial for its therapeutic efficacy: A single 0.3 g/kg dose of triheptanoin reaches a C_max of 178.9 µmol/L, with a T_max 0.5 h, and an AUC of 336.5 µmol\*h/L. A single 0.4 g/kg dose of triheptanoin reaches a C_max of 259.1 µmol/L, with a T_max 0.8 h, and an AUC of 569.1 µmol\*h/L. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Triheptanoin is an important consideration for its dosing schedule: Due to multiple peak concentrations of the heptanoate metabolite, the half life of triheptanoin could not be determined. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Triheptanoin exhibits a strong affinity for binding with plasma proteins: Triheptanoin is approximately 80% protein bound in plasma, likely serum albumin. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Triheptanoin from the body primarily occurs through: Triheptanoin is minimally eliminated in the urine. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Clearance:

The clearance rate of Triheptanoin is a critical factor in determining its safe and effective dosage: A single dose of 0.3 g/kg results in a mean apparent clearance of 6.05 L/h/kg for heptanoate. A single dose of 0.4 g/kg results in a mean apparent clearance of 4.31 L/h/kg for heptanoate. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Triheptanoin exerts its therapeutic effects through: Triheptanoin is a source of medium chain fatty acids for patients with lc-FAODs. It has a moderate duration of action and a wide therapeutic window. Patients should be counselled regarding the risk of feeding tube dysfunction and intestinal malabsorption due to pancreatic insufficiency. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Triheptanoin functions by: Triheptanoin is a source of heptanoate fatty acids, which can be metabolized without the enzymes of long chain fatty acid oxidation. In clinical trials, patients with lc-FAODs treated with triheptanoin experienced improvements in hypoglycemia, cardiomyopathy, and rhabdomyolysis. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Classification:

Triheptanoin belongs to the class of organic compounds known as triacylglycerols. These are glycerides consisting of three fatty acid chains covalently bonded to a glycerol molecule through ester linkages, classified under the direct parent group Triacylglycerols. This compound is a part of the Organic compounds, falling under the Lipids and lipid-like molecules superclass, and categorized within the Glycerolipids class, specifically within the Triradylcglycerols subclass.

Categories:

Triheptanoin is categorized under the following therapeutic classes: Alimentary Tract and Metabolism, Caloric Agents, Glycerides, Lipids, Medium-chain Triglycerides, Triglycerides, Various Alimentary Tract and Metabolism Products. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.