Tamotsu Yamazaki

Effects of AN-132 and quinidine, antiarrhythmic agents, on plasma digoxin concentrations in rats

Abstract— The effects of AN‐132, 3‐(diisopropylaminoethylamino)‐2′,6′‐dimethylpropionanilide.2H3PO4, on chloroform‐induced arrhythmias and plasma digoxin concentrations have been compared with those of quinidine in rats. AN‐132 (0.01–3 mg kg−1) administered orally significantly inhibited the incidence of cardiac arrhythmias in a dose‐related fashion. A single dose of digoxin (1 mg kg−1) given orally for 7 consecutive days was followed, on day 8, orally by digoxin alone, or together with AN‐132 (50, 100 and 200 mg kg−1) or quinidine (25 and 50 mg kg−1). The AUC0‐24 and Cmax of plasma digoxin were enhanced significantly by co‐administration of quinidine, but not by AN‐132.

Effects of nicorandil and verapamil, antianginal agents, on plasma digoxin concentrations in rats and dogs

The effects of equihypotensive doses of nicorandil and verapamil on plasma digoxin concentrations have been assessed in rats and dogs. In a single digoxin dose study, digoxin (1 mg kg−1) alone, or in combination with nicorandil (5 mg kg−1) or verapamil (25 mg kg−1) was given orally to rats. When given chronically to rats, a single dose of digoxin (1 mg kg−1) orally for 7 consecutive days was followed, on day 8, by digoxin alone, or together with nicorandil (5 mg kg−1) or verapamil (25 mg kg−1). In dogs, a loading dose of digoxin (50 μg kg−1) was given orally on day 1, then 25 μg kg−1 was administered for the following 6 days. On day 8, digoxin (50 μg kg−1) was given with nicorandil (5 mg kg−1) or verapamil (20 mg kg−1). In rats, the AUC0–24 and Cmax of plasma digoxin were enhanced significantly by coadministration of verapamil, but not by nicorandil. In dogs, verapamil significantly increased the Cmax of plasma digoxin, but not the AUC. Nicorandil had no effect on either parameter.

CARDIOHAEMODYNAMIC EFFECTS OF LONG‐TERM INTRAVENOUS ADMINISTRATION OFW‐(2‐HYDROXYETHYL)NICOTINAMIDE NITRATE (SG‐75), A POTENT CORONARY VASODILATOR: COMPARISON WITH GLYCERYL TRINITRATE

1. Cardiohaemodynamic changes have been studied in beagle dogs treated with intravenous injections of either 300 μg/kg of N‐(2‐hydroxyethyl) nicotinamide nitrate (SG‐75) or 30 μg/kg of glyceryl trinitrate three times a day for 1 ‐2 months. Throughout the experimental period, no significant changes in general behaviour, body weights and plasma levels of enzymes and substrates were observed in either the SG‐75‐ or glyceryl‐trinitrate‐treated groups.