Anticholinergic activity in the serum of patients receiving maintenance disopyramide therapy

The steady state serum levels of disopyramide and its metabolite, mono-N-dealkylated disopyramide (MND) were measured by gas-liquid chromatography in 40 patients receiving maintenance disopyramide treatment. The levels were mean 3.11 micrograms/ml +/- 0.28 (s.e. mean) and 0.9 micrograms/ml +/- 0.13 (s.e. mean), respectively. A radioreceptor assay was used for the quantitation of the anticholinergic activity of disopyramide and its metabolite in the same serum samples. The serum levels of anticholinergic activity varied between 0 and 6.7 ng/ml when measured as atropine equivalent (mean 1.88 +/- 0.26, s.e. mean, ng/ml). After a single oral dose of disopyramide the serum anticholinergic activity was, however, not detectable or very low. There was a significant correlation between disopyramide concentrations in serum and the serum anticholinergic activity (r = 0.655, P less than 0.001). No correlation was found between MND concentrations and the anticholinergic activity arguing against the role of MND causing antimuscarinic side effects. The affinity of MND for the muscarinic receptors in vitro was also lower than that of disopyramide.