Macimorelin

Macimorelin Uses, Dosage, Side Effects, Food Interaction and all others data.

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.

Macimorelin
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Macimorelin
Availability	Prescription only
Generic	Macimorelin
Macimorelin Other Names	Macimorelin
Related Drugs	insulin regular, Humulin R, Novolin R, Macrilen
Weight	60mg
Type	Oral granule for reconstitution
Formula	C₂₆H₃₀N₆O₃
Weight	Average: 474.565 Monoisotopic: 474.23793885
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Macimorelin is a medication used to treat adult growth hormone deficiency.

Indicated for the diagnosis of adult growth hormone deficiency (AGHD) .

Macimorelin is also used to associated treatment for these conditions: Adult Onset Growth Hormone Deficiency

How Macimorelin works

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.

Toxicity

Macimorelin has not shown to demonstrate mutagenic properties according to bacterial assays. It also did not induce any mutations or clastogenic effects in mouse lymphoma cells with or without metabolic activation. Studies assessing the carcinogenic potential or effect on fertility of macimorelin have not been conducted .

Food Interaction

Avoid St. John's Wort. This herb induces the CYP3A metabolism of macimorelin and may reduce its serum concentration, which may cause a false-positive test result.
Take on an empty stomach. Fast for at least eight hours before taking macimorelin.

[Moderate] ADJUST DOSING INTERVAL: Food reduces the oral bioavailability of macimorelin.

According to the product labeling, administration with a liquid meal decreased macimorelin peak plasma concentration (Cmax) and systemic exposure (AUC) by 55% and 49%, respectively, compared to administration under fasting conditions (i.e., for at least 8 hours).

MANAGEMENT: Macimorelin should be administered after fasting for at least 8 hours.

Macimorelin Disease Interaction

Moderate: arrhythmias

Volume of Distribution

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 .

Elimination Route

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 .

Half Life

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 .