Digoxin therapeutics: straightening out the facts

This article is essentially a review of the pharmacokinetic rationale behind digoxin therapeutics. It covers the various approaches to digoxin therapeutics including the therapeutic endpoint and the use of plasma concentrations of digoxin, the various problems involved in dosage design (particularly pharmacokinetic variability), prescribing aids (and their total impact on the variability in plasma concentrations achieved), and finally, the alternative use of blood-level data to separate and identify the variation in absorption-disposition from the variation in the relationship of plasma concentration to effect. On the basis of available data, it is concluded that by both turning to prescribing aids that have been formulated from clinical data gathered under more nearly ideal conditions and selecting the dosage to give a target concentration based on single measurements of serum digoxin concentrations, may not result in much improvement over fixed or intuitive dosing as far as achieving a predetermined target level is concerned. The probable causes for this lack of precision are explored, and finally an optimum approach to digoxin therapeutics is defined.