Iisalo E, Aaltonen L
Br J Clin Pharmacol. 1984 Mar;17(3):325-9. doi: 10.1111/j.1365-2125.1984.tb02348.x.
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.
采用气液色谱法测定了40例接受丙吡胺维持治疗患者的丙吡胺及其代谢产物单-N-脱烷基丙吡胺（MND）的稳态血清水平。其水平分别为平均3.11微克/毫升±0.28（标准误均值）和0.9微克/毫升±0.13（标准误均值）。采用放射受体分析法对同一血清样本中丙吡胺及其代谢产物的抗胆碱能活性进行定量。以阿托品当量计，血清抗胆碱能活性水平在0至6.7纳克/毫升之间变化（平均1.88±0.26，标准误均值，纳克/毫升）。然而，单次口服丙吡胺后，血清抗胆碱能活性无法检测到或非常低。血清中丙吡胺浓度与血清抗胆碱能活性之间存在显著相关性（r = 0.655，P<0.001）。未发现MND浓度与抗胆碱能活性之间存在相关性，这表明MND并非导致抗毒蕈碱副作用的原因。MND在体外对毒蕈碱受体的亲和力也低于丙吡胺。
