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

Abstract

AbstractBackgroundIntranasal 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.MethodsIn 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).ResultsFor 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).ConclusionsOur 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.