Interactions between digitoxin and some antiarrhythmic drugs.
In the present study the pharmacokinetic interactions between digitoxin and the antiarrhythmic drugs amiodarone, mexiletine and propafenone have been examined. Experiments were performed on rabbits in which serum digitoxin concentration was used as indicator to detect drug interactions. The radioimmunoassay "Coat-A-Count" procedure of DPC was used for the quantitative measurement of digitoxin. It was determined that in order to achieve a considerable level of serum digitoxin, it was necessary to administer a multiple dose rather than the one tolerated by humans. It was also observed that serum contained digitalis like immunoreactive factor(s) (DLIF) measured as digitoxin. The mean (+/- SE) digitoxin equivalent value of the DLIF, measured by the "Coat-A-Count" radioimmunoassay in the serum of rabbits (n = 34) was 4.15 +/- 0.059 ng/ml. Each of the three antiarrhythmic drugs increased serum digitoxin levels; its values were almost double in relation to the control group where only digitoxin was administered. This increased digitoxin value was detected one hour after administration of the first dose of the antiarrhythmic drug and remained at a higher level than that of the control group for 6-8 hours. Rabbits given a single high dose of digitoxin and some of the antiarrhythmic drugs and those given a small dose of digitoxin for only four days, presented a retrogressive increase of digitoxin level in serum 5-6 days later. This mechanism needs to be further investigated.
Sphakianaki
E
E
Department of Pharmacology, Medical Faculty, Aristotelian University of Thessaloniki, Greece.
Tsouderos
I
I
Morali
A
A
Kokkas
B
B
Papadopoulos
K
K
Kotoula
M
M
Paradelis
A
A
D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004074:Digitoxin / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D008297:Male; D008801:Mexiletine / Q000494:pharmacology; D011405:Propafenone / Q000494:pharmacology; D011817:Rabbits; D011863:Radioimmunoassay
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D011405:Propafenone; D004074:Digitoxin; D000638:Amiodarone