Capparelli E V, DiPersio D M, Zhao H, Kluger J, Chow M S
Drug Information Center, Hartford Hospital, CT 06115.
J Clin Pharmacol. 1988 Apr;28(4):306-11. doi: 10.1002/j.1552-4604.1988.tb03148.x.
The pharmacokinetics of the controlled-release preparation of disopyramide phosphate (Norpace CR, Searle Laboratories, Chicago, IL) were studied in ten patients with cardiac arrhythmias. Multiple-serum disopyramide concentrations were obtained after a 300-mg oral dose. Each patient then received chronic oral therapy with the controlled-release preparation (400 to 1000 mg/day) on an every-12-hour schedule. At steady state, disopyramide trough concentrations were obtained. Serum disopyramide concentrations were determined by high performance liquid chromatography. The regimen was well tolerated by all patients. The mean (+/- SD) time to maximum concentration, maximum concentration, and concentrations 11 and 24 hours after the initial dose were 5.5 +/- 1.3 hours and 2.8 +/- 0.8, 2.0 +/- 0.9, and 1.2 +/- 0.5 micrograms/mL, respectively. A low Cmax to trough concentration ratio of 1.35 +/- 0.26 was observed after the initial dose. Linear regression analysis of the serum disopyramide concentrations 11 hours after initial dose (trough) versus trough concentrations at steady state (dose adjusted) showed a strong correlation (r = 0.87, intercept = 0.03, and slope = 1.9). Regression analysis also showed a strong relationship between the area under the curve (AUC) from time 0 to 11 hours after the initial dose and the trough at steady state (r = 0.86).
The controlled-release preparation of disopyramide, when administered every 12 hours in patients with cardiac arrhythmias, should produce low peaks to trough fluctuations. Because disopyramide concentrations after the initial dose correlate well with trough concentrations at steady state, these concentrations may provide a simple and convenient method for prospective monitoring of disopyramide therapy in patients receiving the controlled-release preparation.
对10例心律失常患者研究了磷酸丙吡胺控释制剂（Norpace CR，Searle Laboratories，芝加哥，伊利诺伊州）的药代动力学。口服300 mg剂量后获得多次血清丙吡胺浓度。然后每位患者按每12小时一次的给药方案接受控释制剂的长期口服治疗（400至1000 mg/天）。在稳态时，获得丙吡胺谷浓度。血清丙吡胺浓度通过高效液相色谱法测定。所有患者对该给药方案耐受性良好。初始剂量后达到最大浓度的平均（±标准差）时间、最大浓度以及11和24小时后的浓度分别为5.5±1.3小时、2.8±0.8、2.0±0.9和1.2±0.5μg/mL。初始剂量后观察到低的峰谷浓度比，为1.35±0.26。对初始剂量后11小时（谷值）的血清丙吡胺浓度与稳态时（剂量调整后）的谷浓度进行线性回归分析显示出强相关性（r = 0.87，截距 = 0.03，斜率 = 1.9）。回归分析还显示初始剂量后0至11小时曲线下面积（AUC）与稳态时谷浓度之间存在强相关性（r = 0.86）。
丙吡胺控释制剂在心律失常患者中每12小时给药一次时，应产生低的峰谷波动。由于初始剂量后的丙吡胺浓度与稳态时的谷浓度相关性良好，这些浓度可为接受控释制剂的患者前瞻性监测丙吡胺治疗提供一种简单便捷的方法。
