Pharmacokinetics and pharmacodynamics of intravenous and oral (S)-ketamine: Investigating metabolite contribution to subjective effects.
British Journal of Clinical Pharmacology July 1, 2026 Marije E. Otto, Gabriël E. Jacobs, Joost C Van Mechelen et al.
Oral administration of (S)-ketamine for treatment-resistant depression (TRD), as alternative to the registered intranasal or off-label intravenous administrations, has high potential. However, it is characterized by an extensive first-pass metabolism, resulting in low (S)-ketamine exposure and high levels of active metabolites, including (S)-norketamine and (S)-hydroxynorketamine. The relative...