Download Advances in Pharmacology by Silvio Garattini and Parkhurst A. Shore (Eds.) PDF
By Silvio Garattini and Parkhurst A. Shore (Eds.)
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For drugs used in chronic diseases, the period of laboratory observation should be extended to 1 year in rats and 6 months in dogs. Drugs for over-the-counter purchase may require up to 2 years of study in rats and dogs. Experience has shown that meaningful drug toxicity which can be recognized by the routine experiments, with few exceptions, develops within 90 days of treatment. It is the opinion of many workers in the field that for most drugs, 3 to 6 months study in rats and dogs should procure sufficient information to safeguard against specific organ toxicity.
Low in protein and choline, or high in saturated fat or cholesterol, and observe drug effects on structure and fat content of the liver (DiLuzio and Zilversmit, 1956; Zbinden and Studer, 1957). Potentiation of the ethionine liver damage by chlorpromazine has been described by Popper et al. (1957). Using the same technique, we found that chlorprothixene did, and the chemically related amitriptyline did not potentiate ethionine liver damage. Neither drug has been associated with jaundice in man.
Injections or oral administration by tube and capsules are usually given once per day unless vomiting or other acute drug effects necessitate divided doses. For economic reasons DRUG TOXICITY 25 it has become an accepted practice not to administer the drug on weekends. c. Dosage and number of dose levels. Three or a t most four dose levels and a control group are sufficient. Simultaneous testing of a chemically or pharmacologically related standard drug is often very useful (Grupp and Oser, 1960) but adds considerably to the cost of the experiment.