Pyridostigmine
Pyridostigmine. Reversible peripheral acetylcholinesterase inhibitor — quaternary ammonium prevents BBB penetration → no CNS effects. First-line… Oral half-life 1.6 h.
Reversible peripheral acetylcholinesterase inhibitor — quaternary ammonium prevents BBB penetration → no CNS effects. First-line symptomatic therapy for myasthenia gravis. Cholinergic crisis at overdose; nicotine-receptor desensitization under-treats severe cases.
PK: the best-supported record in its group — F 14.3% and the intravenous half-life of 97 minutes are both verbatim. THE STORED ABSORPTION RATE WAS STRUCTURALLY IMPOSSIBLE, NOT MERELY UNSOURCED: its own cited paper diagnoses flip-flop outright, "Mean t1/2 of the plasma level decline after oral dosing was 200 minutes, twice as long as the terminal elimination t1/2 after intravenous infusion (97 minutes). Thus absorption may proceed at a slower rate than elimination" — so the rate must be BELOW the elimination constant of 0.429, and 1.0 asserted more than double it. The correct value derived from that same 200 minutes is 0.208, flagged as derived. The oral half-life of 3.5 h is likewise the absorption showing through and is replaced by the disposition value on both routes. V 80 L becomes an intravenous-derived 1.43 L/kg, though from only two subjects, and the trap on that paper is logged: its ORAL 1.64 L/kg is apparent and must never be paired with the measured bioavailability. UNIQUELY IN ITS GROUP THE EFFECT IS NOT DECOUPLED — "The pharmacodynamic effect does not lag significantly from the plasma concentration" — so having no effect compartment is correct.
Pharmacokinetics
- Oral — t½ 1.6 h · F 14% · ka 0.208 h⁻¹ · Vd 100.1 L
- IV — t½ 1.6 h · F 100% · Vd 100.1 L
Sources: PMID:3987173, PMID:7439266, PMID:9549661