Pharmacology: Properties and Effects: 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 nondepolarizing muscle relaxants only. It has a synergistic effect on depolarizing muscle relaxants.
Pharmacokinetics: Absorption: Pyridostigmine eg, 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 hrs after administration of pyridostigmine 120 mg. 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 hrs are given for the elimination half-life (t½). This can, however, be prolonged up to 3 times over in individual cases. Mean plasma clearance in healthy volunteers is given as 0.36-0.65 L/kg/hr. 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 the 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 t½ can increase approximately 4-fold and plasma clearance can fall by up to around 1/5 in the case of age- or disease-induced kidney failure.