%0 Case Reports
%T Increasing the bioavailability of oral esketamine by a single dose of cobicistat: A case study.
%A Vos CF
%A Hemminga WL
%A Aarnoutse RE
%A Ruhé HG
%J Pharmacotherapy
%V 44
%N 6
%D 2024 Jun 31
%M 38819020
%F 6.251
%R 10.1002/phar.2942
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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).<BR><B>RESULTS: </B>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).<BR><B>CONCLUSIONS: </B>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.