Macimorelin API Manufacturers

General Description:

Macimorelin, identified by CAS number 381231-18-1, is a notable compound with significant therapeutic applications. Macimorelin, a novel and orally active ghrelin mimetic that stimulates GH secretion, is used in the diagnosis of adult GH deficiency (AGHD). More specifically, macimorelin is a peptidomimetic growth hormone secretagogue (GHS) that acts as an agonist of GH secretagogue receptor, or ghrelin receptor (GHS-R1a) to dose-dependently increase GH levels . Growth hormone secretagogues (GHS) represent a new class of pharmacological agents which have the potential to be used in numerous clinical applications. They include treatment for growth retardation in children and cachexia associated with chronic disease such as AIDS and cancer. Growth hormone (GH) is classically linked with linear growth during childhood. In deficiency of this hormone, AGHD is commonly associated with increased fat mass (particularly in the abdominal region), decreased lean body mass, osteopenia, dyslipidemia, insulin resistance, and/or glucose intolerance overtime. In addition, individuals with may be susceptible to cardiovascular complications from altered structures and function . Risk factors of AGHD include a history of childhood-onset GH deficiency or with hypothalamic/pituitary disease, surgery, or irradiation to these areas, head trauma, or evidence of other pituitary hormone deficiencies . While there are various therapies available such as GH replacement therapy, the absence of panhypopituitarism and low serum IGF-I levels with nonspecific clinical symptoms pose challenges to the detection and diagnosis of AGHD. The diagnosis of AGHD requires biochemical confirmation with at least 1 GH stimulation test . Macimorelin is clinically useful since it displays good stability and oral bioavailability with comparable affinity to ghrelin receptor as its endogenous ligand. In clinical studies involving healthy subjects, macimorelin stimulated GH release in a dose-dependent manner with good tolerability . Macimorelin, developed by Aeterna Zentaris, was approved by the FDA in December 2017 under the market name Macrilen for oral solution.

Indications:

This drug is primarily indicated for: Indicated for the diagnosis of adult growth hormone deficiency (AGHD) . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Macimorelin undergoes metabolic processing primarily in: Macimorelin predominantly undergoes CYP3A4-mediated metabolism according to an *in vitro* human liver microsomes study . This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Macimorelin are crucial for its therapeutic efficacy: Macimorelin is a novel, synthetic ghrelin agonist, which is readily absorbed from the gastrointestinal tract . The maximum plasma concentration (Cmax) was observed between 0.5 and 1.5 hours following oral administration of 0.5mg/kg macimorelin to patients with AGHD under fasting for at least 8 hours. Higher doses of drug demonstrate a dose-proportional increase in plasma concentrations . A liquid meal decreased the macimorelin Cmax and AUC by 55% and 49%, respectively . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Macimorelin is an important consideration for its dosing schedule: The mean terminal half-life (T1/2) is 4.1 hours following administration of a single oral dose of 0.5 mg macimorelin/kg body weight in healthy subjects . This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Macimorelin is distributed throughout the body with a volume of distribution of: Following a single oral dose of 0.5 mg/kg macimorelin, the mean volume of distribution of the central compartment is 5,733.4 ± 565.7L . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Macimorelin is a critical factor in determining its safe and effective dosage: Following a single oral dose of 0.5 mg/kg macimorelin, the mean clearance over the fraction absorbed (Cl/F) was 37,411.0 ± 4,554.6 mL/min . It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Macimorelin exerts its therapeutic effects through: Maximum GH levels from stimulation are observed between 30 to 90 minutes after administration of macimorelin . Increase in the QTcF interval may be observed from macimorelin administration . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Macimorelin functions by: Ghrelin is an endogenous ligand for the GH secretagogue receptor that is also called the ghrelin receptor (GHS-R1a). Upon activation of the receptor, ghrelin serves to increase growth hormone (GH) secretion. Macimorelin mimics the actions of ghrelin by stimulating GH release. As a synthetic agonist, it activates growth hormone secretagogue receptors present in the pituitary and hypothalamus. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Macimorelin belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond, classified under the direct parent group Dipeptides. This compound is a part of the Organic compounds, falling under the Organic acids and derivatives superclass, and categorized within the Carboxylic acids and derivatives class, specifically within the Amino acids, peptides, and analogues subclass.

Categories:

Macimorelin is categorized under the following therapeutic classes: Amino Acids, Amino Acids, Aromatic, Amino Acids, Cyclic, Amino Acids, Peptides, and Proteins, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 Substrates, Diagnostic Agents, Growth Hormone Secretagogue Receptor Agonist, Growth Hormone Secretagogue Receptor Agonists, Heterocyclic Compounds, Fused-Ring, Highest Risk QTc-Prolonging Agents, QTc Prolonging Agents, Tests for Pituitary Function. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.