Pyridostigmine metabolism in man

Abstract

Observations of myasthenic patients given oral pyridostigmine and 14 C‐pyridostigmine by intramuscular injection were designed to determine the excretion in urine of unchanged pyridostigmine and its metabolites. Paper chromatography of urine revealed the presence of three metabolites in addition to pyridostigmine. The unchanged drug and its major metabolite were isolated from the urine of a patient given oral doses with the use of the combined techniques of ion‐exchange chromatography, electrophoresis, and paper chromatography. Pyridostigmine and 3‐hydroxy‐N“methyl pyridinium thus isolated were characterized by ultraviolet spectra and mass spectra and estimated by a reverse isotope‐dilution method. It is suggested that the problems of chronic overdosage with pyridostigmine are related to the possible accumulation of some of these substances in patients who are treated for prolonged periods with high doses of pyridostigmine.