Moclobemide
Moclobemide. Short-acting reversible MAO-A inhibitor — competitively binds MAO-A (and weakly MAO-B at high doses) → raises synaptic serotonin… Oral half-life 2 h.
Short-acting reversible MAO-A inhibitor — competitively binds MAO-A (and weakly MAO-B at high doses) → raises synaptic serotonin, noradrenaline, and dopamine without the irreversible enzyme destruction caused by classical MAOIs. Reversibility plus MAO-A selectivity means dietary tyramine can still be metabolised by intestinal MAO-B and by displacement of moclobemide, so the 'cheese reaction' risk is substantially lower than with phenelzine/tranylcypromine at label doses. Serotonin-syndrome interactions remain relevant.
F 0.9 CONFIRMED verbatim but read the population: PMID:3665338 states "The absolute oral bioavailability increased from 0.56 after the first oral dose to 0.86 and 0.90 after the first and second weeks of administration, respectively". 0.90 is the SECOND-WEEK STEADY-STATE value; single-dose absolute F is 0.56, a 1.6-fold fork inside one sentence. Anyone rendering a single dose from this row is using a chronic-dosing F. PK: A THREE-STATE RECORD ASSEMBLED FROM ONE PAPER. Its cited review contains no numeral at all, and every stored value traces instead to a study that was never cited: "clearance, 39.4 (15%) and 29.1 (12%) L/hr; elimination half-life, 1.60 (15%) and 2.00 (18%) hours; and volume of distribution at steady state, 84.3 (11%) and 80.7 (15%) L. The absolute oral bioavailability increased from 0.56 after the first oral dose to 0.86 and 0.90". THE VOLUME WAS THE DRUG-NAIVE FIRST INFUSION, THE HALF-LIFE WAS AFTER FIFTEEN DAYS OF DOSING, AND THE BIOAVAILABILITY WAS NEITHER. All three now come from the steady state, which is the clinically relevant one for a drug taken daily. MOCLOBEMIDE IS NOT A CARBAMAZEPINE AND MUST NOT BE STRIPPED: its ELIMINATION parameter moves only 1.25-fold on repeated dosing, squarely in the band that kept efavirenz and rifabutin, even though total exposure moves about threefold — "Mean accumulation factors for moclobemide during the first week were 1.85 for Cmax and 3.0 for AUC ... higher than predicted from single-dose characteristics". THAT IS REPRESENTABLE HERE BECAUSE THE SOLVER HAS SEPARATE BIOAVAILABILITY AND ELIMINATION SLOTS, where carbamazepine had to put the whole effect on one. The record fails the peak-to-exposure floor by 1.77x and preserves exposure; the previous mix landed the peak within 17% only because a steady-state bioavailability was being applied to a single dose.
Pharmacokinetics
- Oral — t½ 2 h · F 90% · Vd 80.7 L
Sources: PMID:8582117, PMID:3665338, PMID:2248087