Teriparatide has no effect on the calcium-mediated pharmacodynamics of digoxin.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Teriparatide, 20 microg subcutaneously, does not alter the cardiac effect of digoxin.
Benson
Charles T
CT
Lilly Laboratories for Clinical Research, Indiana University Hospital & Outpatient Center, Indianapolis, 46202-5250, USA.
Voelker
James R
JR
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D015220:Calcium Channels / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D018592:Cross-Over Studies; D004077:Digoxin / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D019379:Teriparatide / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D015220:Calcium Channels; D002316:Cardiotonic Agents; D019379:Teriparatide; D004077:Digoxin