Τόμος 9 (1991) – Τεύχος 2 – Άρθρο 6 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 9 (1991) – Issue 2 – Article 6 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

9: 118-125 (1991)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

9: 118-125 (1991)

digoxin, verapamil, nifedipine, fendiline, diltiazem, cinnarizine, lidoflazine, drug interactions

In the present study the possibility of drug interaction during simultaneous administration of digoxin and calcium channel blockers was examined. For this purpose 49 digitalized patients were studied. They were divided in 6 groups. Each group was administered concur­rently of the following: verapamil, nifedipine, fendiline, diltiέzem, cinnarizine or lidoflazine. Blood samples were taken from all patients and serum digoxin concentrations were measured using an immuno-enzymatic method (ELISA). Digoxin concentrations were statistically cor­related for all groups.

From the results observed the following conclusions can be drawn:

1. In the digoxin-verapamil group, digoxin concentrations were significantly increased, an effect which can be possibly attributed to a decrease in the renal tubular secretion of digoxin. The same result, but in smaller degree, was observed in the group receiving diltiazem. Since digoxin, verapamil and diltiazem have comparable electrophysiologic actions on the sinus node as well as on the atrioventricular node it can be concluded that increased digoxin toxicity may occur as a result of the interaction between these drugs.
2. In the digoxin-nifedipine group a moderate increase in the serum digoxin concentrations was observed.
3. In contrast, in the fendiline, cinnarizine and lidoflazine groups no significant increase of the serum digoxin concentrations was observed.

In summary, we can conclude that:

1. There is an interaction between digoxin-verapamil and digoxin-diltiazem.
2. There is an increase of serum digoxin concentrations during the administration of nifedipine.
3. Finally, there is no interaction between digoxin and fendiline, cinnarizine or lidoflazine.

Further study of the dose-dependant inter­actions between digoxin and various calcium channel blockers is necessary to enable us to arrive at final conclusions and recommenda­tions.

1. Smith, T.W.: Digitalis toxicity. Epidemiology and clinical use of serum concentration measurements. Am. J. Med. 58: 470 (1975)
2. Α. Παραδέλλης: Aλληλεπιδράσεις φαρμάκων. σελ. 29, 323, University Studio Press, Θεσσαλονίκη, 1985
3. Boston Collaborative Drug Surveillance Program: Ad­verse drug interactions. J.A.M.A. 220: 1238 (1972)
4. Klein, H.O., Lang, R.: ELISA: Α replacement for radio immunoassay? Lancet ii: 406
5. Klein, H.O., Lang, R., Weiss, E., Segni E., Libhaber, C., Guerrero, I., Kaplinsky, Ε.: The influence of verapamil on serum digoxin concentration. Circulation 65: 998 (1982)