How is pyridostigmine metabolized?

Pyridostigmine Metabolism

Pyridostigmine is mainly excreted unchanged by the kidney with minimal hepatic metabolism, requiring dose adjustment in renal impairment. 1

Primary Route of Elimination

• Pyridostigmine undergoes predominantly renal excretion as unchanged drug, with the kidney serving as the primary elimination pathway 1, 2
• The drug exhibits rapid plasma clearance of approximately 0.5 to 1.0 L/h/kg, with a short plasma elimination half-life of 30 to 90 minutes 2
• Lower doses are required in patients with renal disease, and treatment should be titrated to effect based on renal function 1

Pharmacokinetic Characteristics

• The apparent volume of distribution ranges from 0.5 to 1.7 L/kg, reflecting limited tissue penetration due to its quaternary ammonium structure 2
• Oral bioavailability is approximately 10%, indicating substantial first-pass effects or poor absorption from the gastrointestinal tract 2
• Peak plasma concentrations of 40 to 60 micrograms/L occur 1-2 hours after oral administration of 60 mg 2

Metabolic Pathway Details

• Pyridostigmine is a hydrophilic, ionized quaternary ammonium compound that does not readily cross the blood-brain barrier under normal conditions 2, 3
• The drug's quaternary structure limits hepatic metabolism, with most of the dose eliminated renally without significant biotransformation 2, 4
• In Chinese males, apparent clearance was estimated at 136 L/h with an absorption rate constant of 0.68 1/h 5

Clinical Implications of Metabolism

• Severely impaired renal function significantly prolongs elimination, necessitating dose reduction 2
• The short elimination half-life requires frequent dosing (typically every 6-8 hours) to maintain therapeutic effect 2, 5
• Despite the short half-life, intraindividual variations in plasma concentration during a dose interval are small in myasthenic patients on maintenance therapy, likely due to slow gastrointestinal absorption 2

Important Caveats

• Pyridostigmine inhibits the metabolism of mivacurium (a neuromuscular blocking agent), delaying recovery from this drug 6
• Patients with myasthenia gravis treated with cholinesterase inhibitors express reduced plasma cholinesterase activity, risking prolonged neuromuscular blockade with succinylcholine 6
• Methylcellulose has been reported to completely inhibit pyridostigmine absorption 2
• Samples for pharmacokinetic analysis require rapid cooling and addition of internal standard before freezing due to poor stability in plasma and blood 2