Abstract
Many observers have criticized the one-hour method of standardization on account of the failure of complete absorption.
During the course of work on the elimination of digitalis substances, one of us demonstrated the feasibility of making intravenous injections in the frog by the insertion of a fine hypodermic needle into the abdominal vein. It was suggested by Dr. Hatcher that an intravenous method of assay might be evolved upon the frog. Efforts to do so have not been successful but in testing the possibility the idea occurred to us to experiment with an intramuscular method.
Our method is to inject one half the total dose into the thickest part of each thigh, the needle being directed diagonally. The finest needle must be used and hemorrhage avoided. Otherwise the procedures are the same as for the Pharmacopeial method.
Judging by our results, the intramuscular method very largely and, we believe, satisfactorily, solves the difficulty of poor absorption.
Table I summarizes the results. In all cases the intramuscular S.S.S. (systolic standstill) dose has been compared with the lymph sac S.S.S. dose. In no instance has the intramuscular dose been found as large as that by the lymph-sac method.
Tinctures, fluidextracts, digitalin and ouabain have been studied. The last column of the table shows the percentage differences between the lymph sac and the intramuscular S.S.S. doses in corresponding lots of frogs. The effective intramuscular dose of digitalin is 10 per cent. less than by the lymph sac while, with tinctures and fluidextracts, the difference is an average of 18.6 per cent. The intramuscular method gives more constant end points and, therefore, requires less time and material for an assay. Lot I, fluidextracts, illustrates this point. With this preparation we were unable to determine the effective dose on account of poor absorption even with injections of doses 20.6 per cent. above the intramuscular dose. Even ouabain, generally considered as satisfactorily absorbed from the lymph sac, has required an average dosage 15.6per cent. less by the intramuscular method.
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