Delay of cardiac and retinal effects of digoxin following a rapidly attained serum concentration plateau

Abstract

KEY WORDS Digoxin Effect kinetics Colour vision deficienciesMany studies have dealt with the kinetics of the pharmacologic response to digoxin following a single dose (see e.g. Kelman et al. for references). After rapid administration of a single dose, non-equilibrium conditions exist for pharmacokinetic and pharmacodynamic processes; the time course of the effect is out of phase with the time course of plasma concentration. Both the shape of the drug disposition curve and the equilibration delay between plasma and effect site determine the effect kinetics. Therefore, an appropriate pharmacokinetic model is needed to analyse the pharmacodynamics of a drug following bolus injection or oral administration.' The pharmacologic response following a rapidly attained plateau serum level, however, is exclusively determined by the equilibration process between serum concentration and effect. We therefore investigated the time course of digoxin effects (cardiac contractile performance, electrocardiographic parameters) corresponding to a serum concentration plateau of about 4.5 ng ml-' which was attained almost instantaneously from a zero value by controlled infusion. We also evaluated digoxin-induced colour vision impairment after the 4 h digoxin plateau to get some information on the kinetics of the retinal effect in comparison to the cardiac effects.The investigations were a part of an experiment which was designed to test the usefulness of controlled digoxin infusion to achieve rapidly a serum concentration plateau in normal volunteer^.^ The infusion scheme (method of