Mestinon Mechanism of Action

Pharmacology: Pyridostigmine, the active ingredient of Mestinon is a cholinesterase inhibitor. It is characterized by the gentle onset, smooth course, comparatively long duration and gradual decline of its cholinergic action. Pyridostigmine has an antagonistic effect on non-depolarising muscle relaxants only. It has a synergistic effect on depolarizing muscle relaxants.
Pharmacokinetics: Absorption: Pyridostigmine, like other medicines of the same type, is not fully absorbed from the intestinal tract. Bioavailability following oral administration is 3-8%. Considerably higher doses are therefore required for oral as opposed to parenteral administration.
Distribution: Peak plasma concentrations were reached in the fasting state approximately 1.5-2 hours after administration of 120 mg pyridostigmine. The increase in active ingredient is delayed when taken with food. The distribution volume averages 1.4 L/kg body weight. Pyridostigmine is not noticeably bound to plasma proteins and does not cross the blood-brain barrier. Blood plasma levels of 20-60 ng/ml are required in order to obtain the desired therapeutic effect with myasthenia gravis.
Metabolism: Pyridostigmine is metabolized to 3-hydroxy-N-methylpyridine and other unidentified metabolites.
Elimination: Mean values of around 1.5 hours are given for the elimination half life. This can, however, be prolonged up to three times over in individual cases. Mean plasma clearance in healthy volunteers is given as 0.36-0.65 L/kg/h. No confirmed data are available regarding the potential accumulation of unchanged pyridostigmine or active metabolites. Since the dosage must, in any case, be adjusted individually, this point is devoid of practical significance. Pyridostigmine is largely eliminated unchanged (75-81%) via the kidneys. One part (18-21%) appears as the 3-hydroxy-N-methyl-pyridine metabolite in urine. Other unidentified metabolites account for 1-4%.
Kinetics in Specific Clinical Situations: Impaired liver function has no relevant effect on the kinetics of pyridostigmine. The elimination half-life can increase approximately four fold and plasma clearance can fall by up to around one-fifth in the case of age or disease induced kidney failure.