Effects of tedisamil, atenolol and their combination on heart andrate-dependent QT interval in healthy volunteers
Authors: Démolis, Jean-Louis1; Martel, Christine1; Funck-Brentano, Christian1; Sachse, Alisia2; Weimann, Hans-Joseph2; Jaillon, Patrice1
Source: British Journal of Clinical Pharmacology, Volume 44, Number 4, October 1997 , pp. 403-409(7)
Publisher: Blackwell Publishing
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Abstract:
Aims Tedisamil is a new blocker of K+ currents in cardiac tissues, exerts bradycardic effects and has shown clinical efficacy in angina pectoris. Theoretically, when coadministered with a β-adrenoceptor blocker the tedisamil combination could induce dangerous bradycardia and QT interval prolongation. Therefore, the aim of this study was to evaluate the effects of tedisamil and atenolol alone and in combination, on heart rate and QT interval duration at rest and during exercise tests. Methods The effects of tedisamil (100 mg twice daily) and atenolol (50 mg twice daily) on heart rate and QT interval duration were analysed in a three-period crossover study in healthy male volunteers. Results This study showed that tedisamil exerted a significant (P<0.05) bradycardic action at rest (−10 beats min−1; 95% CI: -6 to -15 beats min−1 ) similar to atenolol (−14 beats min−1; -11 to -17) and drug combination (−9 beats min−1; -6 to -12). During exercise, at the highest comparable workload, heart rate did not decrease significantly with tedisamil but decreased significantly with atenolol (−42 beats min−1; -37 to -47) and combination (−47 beats min−1; -41 to 52). Atenolol did not modify QT interval duration. Tedisamil alone and in combination with atenolol increased QT interval duration by 12% (95% CI: 7 to 17%) and 12% (8 to 16) respectively at RR=1000ms, but not at RR<700ms (combination). Tedisamil alone and in combination induced a reverse rate-dependent QT interval prolongation. Conclusions These results indicate that the combination of tedisamil and atenolol is not associated with excessive bradycardia or excessive QT interval prolongation in healthy subjects.Keywords: tedisamil; atenolol; bradycardic agents; QT interval; reverse rate-dependence
Document Type: Research article
DOI: 10.1046/j.1365-2125.1997.t01-1-00603.x
Affiliations: 1: Clinical Pharmacology Unit, Saint-Antoine University Hospital, 184 rue du Faubourg Saint-Antoine, 75571 Paris Cedex 12, France, 2: Solvay Pharma Deutschland Gmbh, Postfach 220, 30002 Hannover, Germany
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