Advances in Pharmacology by Silvio Garattini and Parkhurst A. Shore (Eds.)

By Silvio Garattini and Parkhurst A. Shore (Eds.)

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Liver homogenates and a liver microsome fraction from newborn rabbits contain essentially none of the enzymes involved in N-dealkylation of pyramidon, deamination of amphetamine, hydroxylation of the aromatic ring of acetanilide, oxidation of the ring sulfur of chlorpromazine, side-chain oxidation of hexobarbital, and reduction of the aromatic nitro group of p-nitrobenzoic acid. Within 2 weeks, these enzyme activities appear and they are fully developed a t the age of 4 weeks (Fouts and Adamson, 1959).

This is a rare example of a situation in which adult animals are less resistant than young ones.

Since this is probably also true for man, the investigation of drug toxicity and drug m e t a b o l i s ~in various age groups becomed a matter of consider- DBUQ TOXICITY 39 able practical significance. 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).

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