Although anticholinesterase drugs are generally the first line of treatment of myasthenia gravis (MG), there is still no objective way to determine optimal dosage. Recent studies using analytical methods have provided data on the pharmacokinetics of pyridostigmine. However, the relationship between plasma levels of pyridostigmine and the time course of the therapeutic effect has not been objectively determined. The aim of the present study was to examine this relationship by measuring plasma pyridostigmine levels concurrently with five clinicophysiological parameters of neuromuscular function.
PATIENTSSeven female and three male patients between the ages of 20 and 68 years (E = 37 2 14.2) with histories of MG of from 0.5 to 12 years' duration (sr = 4.4 2 3.7)were studied. Five had mildly generalized, and the other five had moderately severe MG. The last pyridostigmine dose was taken by each patient at least 12 hr before the study.
In 10 patients with myasthenia gravis, we studied the relationship between plasma pyridostigmine levels and five measures of neuromuscular function (NMF) following single oral doses of 60 to 120 mg. The NMF measures were percent decrement of the evoked muscle compound potential, maximum force, force-time integral, vital capacity, and outstretched-arm time. The combined mean improvement was most significant 2 hours after pyridostigmine ingestion and coincided with the peak plasma pyridostigmine levels in eight patients. In seven patients, there was a positive correlation between plasma pyridostigmine levels and the mean percent improvement.
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