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Journal of Pharmacology And Experimental Therapeutics, Vol. 90, Issue 4, 304-312, 1947
Copyright © 1947 by American Society for Pharmacology and Experimental Therapeutics

THE INFLUENCE OF RATE OF ADMINISTRATION UPON THE LETHAL DOSE OF CARDIAC GLYCOSIDES

GEORGE J. MARESH 1 and ALFRED E. FARAH 1

1 Department of Pharmacology, Harvard Medical School, Boston, Mass.

The influence of rate of administration upon the lethal dose of digoxin, oleandrin, and digitoxin has been studied in intact cats. With high rates of administration the lethal dose is high. As the rate of administration is decreased the lethal dose falls until, over a wide range of very slow rates of administration, no further reduction in lethal dose occurs. This smallest lethal dose we refer to in this paper as the minimal lethal dose.

For each glycoside there is a characteristic maximal rate of administration (optimal rate of administration) at which the minimal lethal dose is determined (see table 4).

The methods in general use for determining relative activity of cardiacglycosides do not give the same ratios of activity as the values obtained when the minimal lethal dose is used. The use of the minimal lethal dose for comparison constitutes a reliable basis for relative potency.

Submitted on April 9, 1947






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Copyright © 1947 by the American Society for Pharmacology and Experimental Therapeutics.