Khoo K C, Givens S V, Parsonnet M, Massarella J W
Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
J Clin Pharmacol. 1988 Jan;28(1):29-35. doi: 10.1002/j.1552-4604.1988.tb03097.x.
The effect of oral cibenzoline on steady-state digoxin concentrations was studied in 12 healthy subjects ranging from 41 to 55 years of age. Each subject received an oral dose of 0.25 mg or 0.375 mg digoxin once daily for 27 days. On days 14 to 21, 160 mg of oral cibenzoline were administered concomitantly every 12 hours for a total of 15 doses. Plasma digoxin concentration-time profiles obtained before, during, and after cibenzoline coadministration were compared to determine the effect of oral cibenzoline on steady-state digoxin concentrations. The maximum plasma concentration, time of maximum concentration, area under the curve during a dosing interval and steady-state trough plasma concentration for digoxin, during and after concomitant doses of cibenzoline were similar to those before administration, indicating that cibenzoline did not affect the pharmacokinetics of digoxin. In addition, plasma cibenzoline concentration-time profiles after the first and last dose of cibenzoline were similar to those observed in previous studies in which multiple doses of cibenzoline alone were administered. The results of this study indicate that there is no pharmacokinetic interaction between digoxin and cibenzoline when the two drugs are coadministered to healthy subjects in multiple doses.
在12名年龄在41至55岁之间的健康受试者中研究了口服西苯唑啉对稳态地高辛浓度的影响。每位受试者每天口服一次0.25毫克或0.375毫克地高辛，持续27天。在第14至21天，每12小时同时给予160毫克口服西苯唑啉，共15剂。比较在西苯唑啉联合给药之前、期间和之后获得的血浆地高辛浓度-时间曲线，以确定口服西苯唑啉对稳态地高辛浓度的影响。在联合给予西苯唑啉期间和之后，地高辛的最大血浆浓度、最大浓度出现时间、给药间隔期间的曲线下面积以及稳态谷血浆浓度与给药前相似，表明西苯唑啉不影响地高辛的药代动力学。此外，西苯唑啉第一剂和最后一剂后的血浆西苯唑啉浓度-时间曲线与之前单独给予多剂西苯唑啉的研究中观察到的曲线相似。这项研究的结果表明，当两种药物以多剂量联合给予健康受试者时，地高辛和西苯唑啉之间不存在药代动力学相互作用。
