By Silvio Garattini and Parkhurst A. Shore (Eds.)
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Additional resources for Advances in Pharmacology
DRUG TOXICITY 41 Small variations of the blood pH which occur as a consequence of spontnneous disease may have a considerable influence on the tissue distribution of drugs. blood levels of salicylic acid, phenobarbital, and acetazoleamide are decreased whereas t,he brain contains higher amounts, since a t the more acid pH relatively larger proportions of these drugs, which are acids, are present in the penetrable nonionic form (M. A. , 1961). Such changes may conceivably influence drug toxicity and should certainly be kept in mind in humans where acidosis and alkalosis are frequently observed conditions.
A few data obtained in animal experiments may illustrate the complexity of the problem. I n young rats, the ED,o for barbital hypnosis is significantly lower than in adult animals. This could be due to slower metabolism, poor renal excretion, better absorption, increased permeability of the blood brain barrier, or higher sensitivity of the receptors (Ebert and Yim, 1961). Since barbital plasma levels are lower in young rats, the latter two possibilities are favored; but very often, particularly in newborn animals, absence of drug-metabolizing enzymes is observed.
4/2 strain?.. The*(>:tnimals also do not exhibit excitation after injection of D-amphetamine, but are lethargic regardless of whether they are isolated or crowded in a cage with other mice (Weaver and IZerley, 1962). From these few examples it seems obvious tliat toxicity exlw~-iiiiunts sl-iould be conducted with genetically uniform animal material. If this is not done, an uncontrollcd variability is introduced which may lead to disturbing surpri~05,kuch as an unubually high incidence of spontaneous cataracts or poor weight gain.
Advances in Pharmacology by Silvio Garattini and Parkhurst A. Shore (Eds.)