What question did this study set out to answer?

This research investigates the pharmacokinetics and pharmacodynamics of oral S-ketamine compared to intravenous administration.

June 27, 2026Journal of Psychopharmacology

Pharmacokinetics and pharmacodynamics of orally administered S-ketamine in healthy participants

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Authors

JMJoost van MechelenCentre for Human Drug Research TWTobias A. WielesParnassia Groep LBLaura G. J. M. BorghansCentre for Human Drug Research

Discussion

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Implication

Randomized trial characterizes pharmacokinetic and pharmacodynamic profiles of oral S-ketamine in healthy participants, indicating implications for treatment-resistant depression.

Key Points

This research investigates the pharmacokinetics and pharmacodynamics of oral S-ketamine compared to intravenous administration.
Randomized, double-blind, placebo-controlled, four-way cross-over study with 16 healthy participants.
Participants received single doses of S-KETPO (0.20 and 0.45 mg/kg), S-KETIV (0.40 mg/kg), and placebo.
Plasma concentrations of S-ketamine and metabolites were assessed, alongside safety evaluations and CNS effects up to 24 hours post-dose.
S-KETPO had poor absolute bioavailability of 9-12%.
Peak plasma concentrations for S-KETPO 0.20 mg/kg were 9.81 ng/mL for S-KET and 62.0 ng/mL for S-NOR, while S-KETIV reached 146 ng/mL for S-KET and 55.2 ng/mL for S-NOR (P<0.001).
S-KETIV produced significant CNS effects while S-KETPO showed limited effects and comparable safety.

Cite This Study

Mechelen et al. (2026) studied this question.

synapsesocial.com/papers/6a3f69a5aea7db3c19540616 https://doi.org/10.1177/02698811261456187

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June 27, 2026Journal of Psychopharmacology

Pharmacokinetics and pharmacodynamics of orally administered S-ketamine in healthy participants

View Full Paper

Ask AI

Bookmark

Authors

JMJoost van MechelenCentre for Human Drug Research TWTobias A. WielesParnassia Groep LBLaura G. J. M. BorghansCentre for Human Drug Research

Discussion

Member takes

Implication

Randomized trial characterizes pharmacokinetic and pharmacodynamic profiles of oral S-ketamine in healthy participants, indicating implications for treatment-resistant depression.

Key Points

This research investigates the pharmacokinetics and pharmacodynamics of oral S-ketamine compared to intravenous administration.
Randomized, double-blind, placebo-controlled, four-way cross-over study with 16 healthy participants.
Participants received single doses of S-KETPO (0.20 and 0.45 mg/kg), S-KETIV (0.40 mg/kg), and placebo.
Plasma concentrations of S-ketamine and metabolites were assessed, alongside safety evaluations and CNS effects up to 24 hours post-dose.
S-KETPO had poor absolute bioavailability of 9-12%.
Peak plasma concentrations for S-KETPO 0.20 mg/kg were 9.81 ng/mL for S-KET and 62.0 ng/mL for S-NOR, while S-KETIV reached 146 ng/mL for S-KET and 55.2 ng/mL for S-NOR (P<0.001).
S-KETIV produced significant CNS effects while S-KETPO showed limited effects and comparable safety.

Cite This Study

Mechelen et al. (2026) studied this question.

synapsesocial.com/papers/6a3f69a5aea7db3c19540616 https://doi.org/10.1177/02698811261456187

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