Abstract
The approach, that animal testing may predict pharmacological or toxicological responses in man, is undertaken with the conviction that there is a common plan for all living matter. The major biochemical discoveries of the last thirty years lend support to this conviction. It has been suggested that pharmacologic, toxic, and therapeutic effects of drugs can be directly related to the plasma or tissue concentration of the drug, i. e. the pharmacological responses of various species are similar for equal plasma or tissue levels of the drug. This suggestion is based on evidence that, in many instances, the receptors for a given type of drug are similar in various mammalian species. Gillette (1965), for example, showed that the paralytic effect of zoxazolamine lasted over sixty times longer in the rabbit than in the mouse, but found similar brain levels of the drug in both species at the time the righting reflex was restored. Similar observations with respect to brain levels were made in rats and guinea pigs, and in all four species serum levels were a reflection of brain drug levels. He also reported that carisoprodol had a 10-fold spread in duration of action in various animal species, but plasma levels on restoration of the righting reflex varied only about 30%. Quinn et al. (1958) observed a wide variation in the duration of the anesthetic action of hexobarbital among animal species, but found very little difference in plasma or brain levels of the drug when the animals recovered.
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Mellett, L.B. (1974). The Constancy of the Product of Concentration and Time. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents Part I. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65678-1_17
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DOI: https://doi.org/10.1007/978-3-642-65678-1_17
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