Benson Charles T, Voelker James R
Lilly Laboratories for Clinical Research, Indiana University Hospital & Outpatient Center, Indianapolis, 46202-5250, USA.
Clin Pharmacol Ther. 2003 Jan;73(1):87-94. doi: 10.1067/mcp.2003.7.
Teriparatide (recombinant human parathyroid hormone [1-34]) stimulates bone formation and causes small transient increases in serum calcium concentration. We assessed whether teriparatide causes a change in digoxin pharmacodynamic effects by measuring systolic time intervals and heart rate.
Measurements were made by echocardiographic Doppler that examined 3 systolic time intervals, as follows: QS(2) (time from Q wave on electrocardiogram to the closure of the aortic valve), left ventricular ejection time, and pre-ejection period, all corrected for changes in heart rate. Fifteen healthy subjects (2 men and 13 women) were administered a single subcutaneous teriparatide dose (20 microg) on day 1 and then equilibrated on a daily oral dose of digoxin for 15 days. Subcutaneous placebo and teriparatide, 20 microg, were given in a randomized crossover design with the 14th (day 15) and 15th (day 16) digoxin doses. Serial systolic time interval and heart rate measurements were obtained on days 1, 15, and 16.
After subjects were dosed to steady state with digoxin, there were statistically significant reductions in QS(2) corrected for heart rate (QS(2)c) of 23 to 25 ms and heart rate of 4 to 6 beats/min. However, there was no difference between treatment with digoxin plus placebo versus digoxin plus teriparatide. The study was powered to find a difference in QS(2)c as small as 6 ms (alpha =.05, beta =.2).
Teriparatide, 20 microg subcutaneously, does not alter the cardiac effect of digoxin.
特立帕肽(重组人甲状旁腺激素[1-34])可刺激骨形成,并导致血清钙浓度出现短暂小幅升高。我们通过测量收缩期时间间期和心率,评估特立帕肽是否会引起地高辛药效学效应的改变。
采用超声心动图多普勒进行测量,检查3个收缩期时间间期,如下:QS(2)(从心电图Q波至主动脉瓣关闭的时间)、左心室射血时间和射血前期,所有这些均针对心率变化进行了校正。15名健康受试者(2名男性和13名女性)在第1天接受单次皮下注射特立帕肽剂量(20微克),然后每日口服地高辛进行15天的平衡期。采用随机交叉设计,在第14天(第15天)和第15天(第16天)给予地高辛剂量时,分别皮下注射安慰剂和20微克特立帕肽。在第1天、第15天和第16天进行连续的收缩期时间间期和心率测量。
在受试者用地高辛达到稳态剂量后,校正心率后的QS(2)(QS(2)c)有统计学意义地降低了23至25毫秒,心率降低了4至6次/分钟。然而,地高辛加安慰剂治疗与地高辛加特立帕肽治疗之间没有差异。该研究有能力检测出QS(2)c小至6毫秒的差异(α =.05,β =.2)。
皮下注射20微克特立帕肽不会改变地高辛的心脏效应。