SUMMARY  

• Esketamine (ESK), the s-enantiomer of racemic ketamine, has a 3- to 4-fold higher binding affinity for the N-methyl-D-aspartate (NMDA) receptor than arketamine, the R-enantiomer of ketamine.^1-3
  • Based on reports in the literature suggestive of an effect of ketamine in major depressive disorder (MDD) and the higher potency of ESK allowing for non-invasive intranasal delivery of small volumes of product, Janssen undertook a clinical development program to develop ESK as a potential treatment for challenging to treat subsets of MDD.
• The wide plume angle produced by the nasal spray device used to administer SPRAVATO delivers medication primarily to the respiratory epithelium resulting in rapid and appreciable absorption into the bloodstream (mean total absolute bioavailability, ~48%). The remainder of the dose is swallowed and subjected to first-pass metabolism. The bioavailability of ESK through the nasal route is much higher than that through the oral route (~8%).^4,5
• Clinical trials with SPRAVATO nasal spray demonstrated good local tolerability.^4,6
• Relative to an IV formulation, the nasal route of administration provides a non-invasive and more convenient dosing option for patients and physicians and is associated with a reduced likelihood of dosing errors since it is administered as a multiple of a fixed dosage unit (28 mg for SPRAVATO) instead of a calculated mg/kg dosage.^4,7
  • SPRAVATO is delivered in a metered-dose spray device that underwent numerous human use studies to ensure optimal positioning and consistent dosages are delivered with every administration.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 25 February 2024.