Metabolite cumulation during long‐term oral encainide administration
Metabolite cumulation during long‐term oral encainide administration
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长期口服恩卡尼期间代谢物累积
DOI：
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发表时间：
1982
期刊：
影响因子：
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通讯作者：
R. Winkle
中科院分区：
文献类型：
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作者：
R. Kates;Donald C. Harrison;R. Winkle
在频繁发生复杂性心室异位的患者中检查了恩卡尼及其主要代谢物 O-去甲基恩卡尼 (ODE)、3-甲氧基-ODE (MODE) 和 N-去甲基恩卡尼 (NDE) 的累积情况。服用恩卡尼胺 6 个月后，患者被送往斯坦福大学医院，并停药 24 小时。在此期间，抽取血样来表征药物和代谢物的累积和处置。剂量范围为 100 至 250 mg/天后，恩卡尼、ODE 和 MODE 的平均稳态浓度分别为 56.3、214.6 和 184.6 ng/ml。 ODE/恩卡尼和MODE/恩卡尼的浓度比为5.02±2.61和5.15±4.13。仅在一名患者的血浆中检测到濒死体验。恩卡尼和 ODE 的消除半衰期分别为 1.16 ± 0.5 和 11.41 ± 9.58 小时。 MODE 缓慢消失，24 小时时血浆浓度仍为其平均稳态浓度的 59.8 ± 39.9%。我们的数据表明，恩卡尼的代谢物在长期口服治疗的患者血浆中累积，在评估其临床疗效时必须考虑到这一点。
Cumulation of encainide and its major metabolites, O‐demethylencainide (ODE), 3‐methoxy‐ODE (MODE), and N‐demethylencainide (NDE) was examined in patients with frequent complex ventricular ectopy. After 6 mo on encainide patients were admitted to Stanford University Hospital and the drug was discontinued for 24 hr. During this time blood samples were drawn to characterize the cumulation and disposition of the drug and metabolites. The mean steady‐state concentrations of encainide, ODE, and MODE were 56.3, 214.6, and 184.6 ng/ml after doses ranging from 100 to 250 mg/day. The concentration ratios of ODE/encainide and MODE/encainide were 5.02 ±2.61 and 5.15 ±4.13. NDE was detected in the plasma of only one patient. Elimination half lifes of encainide and ODE were 1.16 ± 0.5 and 11.41 ± 9.58 hr. MODE disappeared slowly and at 24 hr the plasma concentration was still 59.8 ± 39.9% of its mean steady‐state concentration. Our data indicate that the metabolites of encainide cumulate in the plasma of patients on long‐term oral therapy and must be considered when evaluating its clinical efficacy.