Trofinetide

Breast Feeding; Lactation; Milk, Human

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine (Orphan designations)

FDA approved drugs -> Active ingredient

N - Nervous system

QN - Nervous system

Trofinetide works to reduce and alleviate the symptoms of Rett syndrome. It is an analog of [glypromate] or glycine–proline–glutamate (GPE), a naturally occurring protein in the brain and the N-terminal tripeptide of insulin-like growth factor 1 (IGF-1). GPE exhibits neuroprotective properties: it protects neurons from glutamate-mediated excitotoxicity and oxidative stress at nanomolar concentrations. With a longer half-life than GPE, trofinetide is believed to exhibit similar neuroprotective properties.

Most cases of Rett syndrome are associated with loss-of-function mutations in a gene encoding methyl CpG binding protein 2 (MECP2), a DNA binding protein with a role in epigenetic regulation of gene expression. These mutations are believed to lead to synaptic immaturation in the cortex, aberrant metabolism of brain cholesterol resulting in abnormal neuronal development, and abnormal neuronal signaling. Rett syndrome more commonly occurs in girls than boys. The exact mechanism of action of trofinetide in Rett syndrome has not been fully elucidated. In mice studies, GPE improved motor and cardiorespiratory function, increased brain weight, and prolonged the lifespan in MECP2-deficient mice. As a GPE analog, trofinetide similarly attenuated apoptosis and reduced infarct size in a dose-dependent manner in a rat model of hypoxic insult. Trofinetide exerts a multi-faceted action to reduce inflammation, excitotoxicity-induced tissue damage, and apoptosis, thereby protecting the neurons and their surrounding infrastructure.

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TROFINETIDE

Mechanisms of Action [MoA] - Cytochrome P450 3A4 Inhibitors

Mechanisms of Action [MoA] - Organic Anion Transporting Polypeptide 1B1 Inhibitors

Mechanisms of Action [MoA] - Organic Anion Transporting Polypeptide 1B3 Inhibitors

The mechanism of action of trofinetide is as a Cytochrome P450 3A4 Inhibitor, and Organic Anion Transporting Polypeptide 1B1 Inhibitor, and Organic Anion Transporting Polypeptide 1B3 Inhibitor.

Systemic exposure to trofinetide was dose-proportional across the studied dose range. The Tmax is about two to three hours after administration. Based on the mass balance study, at least 84% of the administered oral dose of 12,000 mg trofinetide was absorbed. A high-fat meal had negligible effects on drug exposure and reduced the Cmax by approximately 20%.

Trofinetide is primarily excreted in urine, with minor excretion in feces. Approximately 80% of the dose recovered in urine was in the unchanged parent drug form.

Following oral administration, the apparent volume of distribution of trofinetide in healthy adult subjects was approximately 80 L. Minimal to no accumulation was observed following multiple-dose administration.

No information is available.