Abstract
The relative therapeutic effectiveness of tolysin has been questioned because of the fact that large quantities can be tolerated without toxic effects. This has sometimes been attributed to inefficient absorption. Sufficient evidence has now accumulated to show that tolysin is absorbed in full therapeutic doses in humans, dogs and rats. 1-3 4 To date, however, the margin existing between therapeutic dosage and the limit of absorption has never been clearly demonstrated. Previous investigation has shown that 1,000 Mg./K. of tolysin, when given to rats daily by oral administration was completely absorbed and non-toxic, as evidenced by normal growth rate, absence of symptoms or autopsy findings. 4 The therapeutic response to 25% of this dose is depicted in the following:
Antipyresis in rats was used as the basis for the evaluation of drug action. The animals were fevered by the subcutaneous injection of yeast, using the technique described by Smith and Hambourger. 5 This results in a fever maintained at a fairly constant high level for over 30 hours. Such a lasting fever is a necessity in the study of antipyretics characterized by delayed onset and long duration of action.
During experimentation, the rats were kept in a constant temperature room at 86°F. Drugs were administered by stomach tube, in an acacia suspension, 18 hours after the removal of food. A single experiment consisted in temperature measurements not only on 4 rats for each drug given, but also on 4 fever controls, and 4 room controls. The antipyretic effects recorded are corrected for variations noted in the 2 control groups.
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