Premium
The Effect of Telmisartan on the Steady‐State Pharmacokinetics of Digoxin in Healthy Male Volunteers
Author(s) -
Stangier Joachim,
Su ChungAn P. F.,
Hendriks Maarten G. C.,
Lier Jan J.,
Sollie Frans A. E.,
Oosterhuis Berend,
Jonkman Jan H.G.
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127000004001209
Subject(s) - digoxin , telmisartan , pharmacokinetics , pharmacology , medicine , steady state (chemistry) , chemistry , heart failure , blood pressure
A multiple‐dose, open‐label, two‐period, crossover randomized study was conducted in 12 healthy male volunteers to investigate the effect of multiple‐dose telmisartan on the steady‐state pharmacokinetics of digoxin. On day 1 of a 7‐day medication period, subjects received a loading dose of digoxin 0.5 mg in the morning, followed by an evening dose of digoxin 0.25 mg, either alone or together with telmisartan 120 mg administered in the morning. On the subsequent 6 days, either digoxin 0.25 mg or digoxin 0.25 mg together with telmisartan 120 mg was administered once daily in the morning. Each 7‐day medication period was separated by a washout period of ≥ 14 days. A steady‐state plasma concentration‐time profile was assessed for digoxin during each period and for telmisartan during the period with the combined treatment. Multiple‐dose telmisartan administered with digoxin resulted in higher serum digoxin concentrations than those observed after digoxin given alone. Geometric mean AUC 144–168 , C max , and C min values for digoxin when given in combination with telmisartan were higher by 22%, 50%, and 13%, respectively, compared with values when given alone. However, the 90% confidence interval for the geometric mean of C min was within the predefined 80% to 125% range of no interaction. During combination medication, digoxin t max was shorter and C max /AUC 144–168 increased, suggesting that the rise in digoxin C max may be due to more rapid drug absorption. Study medications were well tolerated, with the incidence, nature, and intensity of adverse events being similar during both medication periods. Also, no changes in vital signs or clinical laboratory tests were observed during the study. Although there was some evidence for a pharmacokinetic interaction between digoxin and telmisartan found in this study, the safety and tolerability of digoxin were unaffected by concurrent administration of telmisartan in the study population. Since any symptoms of overdose are related only to steady state and not peak concentrations and due to the fact that there was a lack of effect on serum trough levels of digoxin in this study, it is unlikely that the findings have any clinical relevance. The magnitude of increase in digoxin concentrations is comparable with increases observed with administration of calcium antagonists, carvedilol, ACE inhibitors such as captopril, and antiarrhythmic drugs such as amiodarone, quinidine, and propafenone. Monitoring of serum digoxin concentrations should be considered when patients first receive telmisartan and in the event of any changes in telmisartan dose.