Formulation Optimization of EVX-101, A Novel Gastro-Retentive Prolonged-Release 5-HTP/Low-Dose Carbidopa Tablet
8 October 2025Inadequate response to antidepressant treatment is a significant issue for many patients with depression. Enhancing brain extracellular serotonin (5-HT) levels beyond those produced by serotoninreuptake inhibitors may treat depression more effectively. Adjunctive treatment with 5-hydroxytryptophan (5-HTP), the natural precursor to 5-HT, can amplify brain serotonin.
However, 5-HTP absorption is restricted to the upper intestine, bioavailability is low, and 5-HTP has a short half-life (t½), making 5-HTP a poor drug. To overcome these pharmacokinetic (PK) limitations, a gastro-retentive (GR) sustainedrelease (SR) formulation is required to maximize absorption producing sustained exposure. Carbidopa inhibits amino acid decarboxylase, the enzyme that converts 5-HTP to 5-HT in the intestine, resulting in decreased first pass metabolism and increased 5-HTP bioavailability.
The development and optimization including PK and safety assessment, of EVX-101 a novel GR SR 5-HTP/carbidopa tablet formulation is described.
