Kinetics and metabolism of intramuscular neostigmine in myasthenia gravis.
Neostigmine kinetics and metabolism were studied after intracellular administration to 8 patients with myasthenia gravis. The plasma neostigmine level declined monoexponentially from 21 +/- 2 to 9 +/- 1 ng/ml between 30 and 120 min. The data were interpreted in terms of a 1-compartment model. Estimates  of plasma half-life (t1/2) ranged from 51.1 to 90.5 min; apparent volume of distribution varied from 32.0 to 60.6 1; and total body clearance from 434 to 549 ml/min. Approximately 80% of the drug was eliminated in urine within 24 hr either as unchanged neostigmine or its metabolites. Approximately 50% of the dose was eliminated as the unchanged drug, 15% as 3-hydroxyphenyltrimethylammonium, and 15% as other unidentified metabolites. The neostigmine t1/2, based on the urinary excretion of the unchanged drug, ranged from 90.2 to 118.7 min. It was concluded that neostigmine was eliminated by renal and extrarenal mechanisms.
D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007700:Kinetics; D008657:Metabolic Clearance Rate; D009157:Myasthenia Gravis / Q000378:metabolism*; D009388:Neostigmine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013997:Time Factors; D014018:Tissue Distribution
D009388:Neostigmine