DETERMINATION OF THE THERAPEUTIC, IRREGULARITY, AND LETHAL DOSES OF CARDIAC GLYCOSIDES IN THE HEART-LUNG PREPARATION OF THE DOG

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The influence of rate of administration on the therapeutic, irregularity, and lethal dose of the glycosides digitoxin, g-strophanthin, digoxin, oleandrin, and lanatoside B has been studied in the HLP of the dog. A reduction of the rate of administration results in a reduction of all these values until the optimal rate of administration is reached. At and below the optimal rate of administration, the minimal therapeutic dose, minimal irregularity dose, and minimal lethal dose are determined. On a molar basis the cardiac glycosides studied have the following order of decreasing potency: g-strophanthin, digoxin, digitoxin, oleandrin, and lanatoside B.

The average ratios of irregularity dose to therapeutic dose and lethal dose to therapeutic dose are the same for all the five glycosides studied. The therapeutic dose is about 15 per cent and the irregularity dose is approximately 60 per cent of the lethal dose.

The authors wish to thank Dr. Otto Krayer for help and advice in the course of this investigation, and Mr. Henry George and Louis Harris for valuable technical assistance.