Ueda C T, Dzindzio B S, Vosik W M
Clin Pharmacol Ther. 1984 Sep;36(3):326-36. doi: 10.1038/clpt.1984.183.
Serum disopyramide determinations and 24-hour Holter monitoring were performed in 20 cardiac subjects with ventricular premature contractions (VPCs) after the first, seventeenth, and thirty-seventh doses of disopyramide, 100 mg (10 subjects; low-dose group) or 200 mg (10 subjects; high-dose group) every 6 hr for 10 days to assess the ability of single- or first-dose data to predict serum disopyramide concentrations at steady state and the relationship between steady-state serum disopyramide concentrations and VPC suppression. Control Holter recordings were made for 48 hr in each subject. There were strong correlations in both groups between data for the AUC over 0 to 6 hr for the first dose (AUC60) and average (C ss) and trough (C min) steady-rate serum disopyramide concentrations after the seventeenth and thirty-seventh doses and the two combined. C ss and C min were related to AUC60 by the following expressions for both dosage groups: C ss = 0.22 AUC60 + 0.90 and C min = 0.20 AUC60 + 0.70. There were good correlations between 6-hr serum disopyramide concentration after the first dose and C ss and C min. There was strong correlation between overall average steady-state serum disopyramide concentration and suppression of VPC frequency. The relationship between VPC suppression and overall average trough serum disopyramide concentration at steady state, on the other hand, was weak.
对20名患有室性早搏（VPC）的心脏疾病受试者进行了血清丙吡胺测定和24小时动态心电图监测。这些受试者每6小时服用100毫克（10名受试者；低剂量组）或200毫克（10名受试者；高剂量组）丙吡胺，共服用10天，分别在首次、第十七次和第三十七次服药后进行上述检测，以评估单次或首次给药数据预测稳态血清丙吡胺浓度的能力，以及稳态血清丙吡胺浓度与室性早搏抑制之间的关系。对每个受试者进行48小时的对照动态心电图记录。在两组中，首次给药后0至6小时的曲线下面积（AUC60）数据与第十七次和第三十七次给药后以及两次给药合并后的平均（Css）和谷值（Cmin）稳态血清丙吡胺浓度之间均存在强相关性。对于两个剂量组，Css和Cmin与AUC60的关系如下：Css = 0.22 AUC60 + 0.90，Cmin = 0.20 AUC60 + 0.70。首次给药后6小时血清丙吡胺浓度与Css和Cmin之间存在良好的相关性。稳态血清丙吡胺总体平均浓度与室性早搏频率抑制之间存在强相关性。另一方面，室性早搏抑制与稳态时总体平均谷值血清丙吡胺浓度之间的关系较弱。
