Increasing the bioavailability of oral esketamine by a single dose of cobicistat: A case study

Background Intranasal esketamine is an approved drug for treatment‐resistant depression (TRD); however, it is costly and may result in specific adverse effects. In this single case study, we explored if oral esketamine can be a suitable alternative. Methods In collaboration with a 39‐year‐old female...

Full description

Saved in:
Bibliographic Details
Published in:Pharmacotherapy 2024-06, Vol.44 (6), p.480-484
Main Authors: Vos, Cornelis F., Hemminga, Wietske L., Aarnoutse, Rob E., Ruhé, Henricus G.
Format: Article
Language:English
Subjects:
Bioavailability
Case studies
Drug dosages
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background Intranasal esketamine is an approved drug for treatment‐resistant depression (TRD); however, it is costly and may result in specific adverse effects. In this single case study, we explored if oral esketamine can be a suitable alternative. Methods In collaboration with a 39‐year‐old female with TRD, we compared plasma concentration curves of intranasal (84 mg) and oral (1, 2 and 4 mg/kg) esketamine. Because oral esketamine has a relatively low bioavailability, it results in a different ratio between esketamine and its primary metabolite noresketamine. To increase the bioavailability of oral esketamine, we co‐administered a single dose of the cytochrome P‐450 (CYP) 3A4 inhibitor cobicistat (150 mg). Results For all doses administered, oral esketamine resulted in lower esketamine but higher noresketamine peak plasma concentrations compared with intranasal treatment. Using oral esketamine it was not possible to generate a similar esketamine plasma concentration curve as with the intranasal treatment, except when combined with cobicistat (esketamine 2 mg/kg plus cobicistat 150 mg). Conclusions Our findings demonstrate that cobicistat effectively increases the bioavailability of oral esketamine. Further research is required in a larger population, especially to investigate the clinical benefit of cobicistat as a booster drug for oral esketamine.
ISSN:0277-0008
1875-9114
DOI:10.1002/phar.2942