Pharmacokinetics of Nasal Esketamine in Patients with Allergic Rhinitis with and Without Nasal Decongestant Pretreatment and in Healthy Subjects with and Without Nasal Corticosteroid Pretreatment.

BACKGROUND AND OBJECTIVES

Nasal esketamine is indicated for the treatment of adults with treatment-resistant depression and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. Primary objectives of this study were to evaluate the effect of nasal decongestant pretreatment in patients with allergic rhinitis and the impact of daily nasal corticosteroid administration by healthy subjects on nasal esketamine pharmacokinetics.

METHODS

Patients with allergic rhinitis self-administered 56 mg of nasal esketamine after pretreatment with nasal oxymetazoline (0.05%) at 1 h before esketamine and without oxymetazoline pretreatment. They were exposed to grass pollen in an allergen challenge chamber to induce allergic rhinitis symptoms at approximately 2 h before each esketamine administration until 1 h after. Healthy subjects self-administered esketamine (56 mg) before and after administration for 16 consecutive days of mometasone (200 µg), with the second esketamine dose administered 1 h after the last mometasone dose. The plasma pharmacokinetics of esketamine and noresketamine were assessed after each esketamine administration. The tolerability of esketamine, including effects on dissociative and potential psychotomimetic symptoms and level of sedation and suicidal ideation and behavior, was evaluated.

RESULTS

The rate of esketamine absorption was slightly greater in patients exhibiting symptoms of allergic rhinitis (decrease in median t from 32 min to 22 min). Increases in esketamine C and AUC were also small (mean, ≤ 21%). The pharmacokinetics of esketamine was not affected by oxymetazoline or mometasone pretreatment. Esketamine was well tolerated when it was administered with or without pretreatment of oxymetazoline or mometasone.

CONCLUSIONS

Patients exhibiting symptoms of rhinitis may receive nasal esketamine spray without dose adjustment. In addition, esketamine may be administered 1 h after using a nasal decongestant or corticosteroid.

TRIAL REGISTRATION

The study was registered in the Clinical Trials (NCT02154334) and EudraCT (2014-000534-38) registries.