Boden W E, More G, Sharma S, Bough E W, Korr K S, Young P M, Shulman R S
Am J Med. 1986 Sep;81(3):425-8. doi: 10.1016/0002-9343(86)90293-7.
The effect of incremental diltiazem dosing during concomitant digoxin administration over a four-week period in eight healthy adult volunteers (mean age, 28 +/- 4 years) was studied. The study group received 0.25 mg of digoxin twice daily for two days, after which they received 0.25 mg daily for the duration of the study. Following baseline electrocardiographic evaluation and measurement of trough digoxin levels, all subjects received 120 mg of diltiazem daily for one week, then 240 mg daily for one week, followed by 360 mg daily for one week. Resting electrocardiographic parameters (heart rate, P-R interval), renal function, electrolyte values, and digoxin and diltiazem concentrations were measured weekly. Daily administration of 360 mg of diltiazem plus 0.25 mg of digoxin resulted in a significant decrease in heart rate (from 68 +/- 9 beats per minute to 61 +/- 10 beats per minute; p less than 0.05), a marginal increase in P-R interval (from 169 +/- 22 msec to 179 +/- 21 msec; p = 0.08), and no significant change in trough serum digoxin concentration (from 0.85 +/- 0.08 ng/ml to 0.90 +/- 0.08 ng/ml; p = NS). The administration of up to 360 mg of diltiazem per day with 0.25 mg of digoxin per day was not associated with significant increases in serum digoxin concentrations in healthy subjects.
研究了8名健康成年志愿者（平均年龄28±4岁）在四周内同时服用地高辛期间递增剂量地尔硫䓬的效果。研究组连续两天每日服用0.25mg地高辛，之后在研究期间每日服用0.25mg。在进行基线心电图评估和测定地高辛谷浓度后，所有受试者每日服用120mg地尔硫䓬，持续一周，然后每日服用240mg，持续一周，接着每日服用360mg，持续一周。每周测量静息心电图参数（心率、P-R间期）、肾功能、电解质值以及地高辛和地尔硫䓬浓度。每日服用360mg地尔硫䓬加0.25mg地高辛导致心率显著降低（从每分钟68±9次降至每分钟61±10次；p<0.05），P-R间期略有增加（从169±22毫秒增至179±21毫秒；p = 0.08），地高辛谷血清浓度无显著变化（从0.85±0.08ng/ml增至0.90±0.08ng/ml；p =无显著性差异）。健康受试者每日服用高达360mg地尔硫䓬加0.25mg地高辛与血清地高辛浓度显著升高无关。
