Esketamine
Esketamine. S-enantiomer of ketamine — ~4× NMDA receptor affinity vs racemate. Intranasal formulation FDA-approved for treatment-resistant… Intranasal half-life 4.6 h.
S-enantiomer of ketamine — ~4× NMDA receptor affinity vs racemate. Intranasal formulation FDA-approved for treatment-resistant depression in conjunction with oral antidepressant. Rapid (hours) antidepressant effect; REMS for dissociation + abuse risk.
PK: THE VOLUME AND THE CLEARANCE ARE STATED IN ONE SENTENCE AND ONLY THE VOLUME WAS TAKEN. "Esketamine volume at steady state and clearance were 752 L and 114 L/h, respectively" — the record kept the 752, dropped the clearance, and paired the volume with an unsourced 8 h, asserting 120.7 L/h against that paper own 211.1 and over-predicting exposure 1.75x. F 0.54 is verbatim and is correctly the 56 mg half of "The absolute bioavailability of 56 and 84 mg of intranasal esketamine is 54 and 51%", matching this record typical dose. THE FIX PRESERVES THE PEAK AND IS STATED AS SUCH: holding the verbatim volume forces the half-life to 4.57 h, whereas restoring the paper clearance at 8 h would need a 1316 L volume and collapse the peak. EVEN THEN THE RECORD CANNOT BE RIGHT ON BOTH — the abstract says "An open linear model for esketamine (THREE COMPARTMENTS)" and the true exposure-to-peak ratio is well below what one compartment can produce. NO TRANSPLANT WITH KETAMINE, the fifth consecutive negative on a marketed enantiomer or metabolite pair: no field matches, and the shared molecular mass is CORRECT because enantiomers have identical mass. ka 4 implied a 59 minute peak against a published 22-32 minutes.
Pharmacokinetics
- Intranasal — t½ 4.6 h · F 54% · ka 7.45 h⁻¹ · Vd 752 L
Sources: PMID:33128208