Comparison of the pharmacokinetic parameters of digoxin and SC4453 a digoxin analogue, following a single bolus i.v. dose and following an infusion preceeded by an i.v. loading dose in the guinea-pig.

The pharmacokinetics of SC4453 was studied in comparison with digoxin both after an intravenous injection and an intravenous infusion following an intravenous bolus injection of a loading dose in the guinea-pig. Doses of 7.8 micrograms/kg for digoxin and 30 micrograms/kg for SC4453 were administered as a bolus. The solutions were prepared from a stock solution (10(-3) M in ethanol-water 7:3) diluted with 0.9% saline. The half lives (t 1/2 beta) for digoxin and SC4453 were 8.4 h and 4.2 h respectively. The apparent volumes of distribution (V1) were respectively 11.4 l/kg and 3.7 l/kg. Using these parameters, an I.V. infusion was administered after an initial bolus injection of a properly calculated loading dose (D* = CpssV1). The perfusion constant K was calculated from the equation: K = CpssV1ke.