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KMID : 0360919730160050054
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Journal of the Korean Medical Association
1973 Volume.16 No. 5 p.54 ~ p.60
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Kim Kyeong-Hwan
Shideman, F.E.
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Abstract
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The activity of the drug metabolizing enzymes in hepatic microsomes has been shown to be markedly influenced by the species, age, sex and other numerous factors. It is known that the fetus and newborn infants are more susceptible than the adult to certain drugs or exogenous agents. Recently occasional studies showed that some of the supersusceptibility in fetus or infants were from the result of the deficiency of the hepatic microsomal enzymes responsible for the metabolism of the corresponding drug. Much of the information concerning the drug metabolism in fetal and developing stages have been largely based on animal experiments and few studies on human fetus were reported.
The present study was undertaken to examine the metabolizing activity of the hepatic microsomal enzymes,N-demethylase of aminopyrine and nitro-reductase of p-nitrobenzoic acid, in human fetus. In addition, the hepatic microsomal enzyme systems in embryonic and postnatal developing stages of rat and chick were compared. The results obtained were summarized as follows.
1. The human fetus obtained by artificial interruption of normal pregnancy on strict medical ground from 14 to 32 weeks of gestational Period. The activities of N-demethylation of aminopyrine and of nitro. reduction of p-nitrobenzoic acid in these fetal liver microsomes were very low but detectable with a wide range of variation in these fetus studied. No correlation was observed between the drug metabolizing, activity and the age of the fetus.
2. In chick embryo, the hepatic aminopyrine anc p-nitrobenzoic acid metabolisms were similarly low with a wide range of variation throughout the development as human fetus. However, the metabolizing activities of these drugs abruptly increased after hat Ching, reaching the maximum value at 2-day old,
3. The hepatic drug metabolizing activity was similarly low in rat embryo as in the chick embryo and human fetus, but slowly increased after the birth. The aminopyrine demethylase activity was progressively increased with age until the value of mature rat where-as the p-nitrobenzoic acid reductase activity attained. its peak value at 30-day old age of the growing rat. There was a marked sex difference in aminopyrine demethylation from the age of 30-day old in this-animal.
4. The induction of hepatic drug metabolising enzyme-was significant in chick embryo after the injection of phenobarbital 5 mg into the amniotic fluid for two days.
5. The percentage of liver weight to body weight was approximately 4.4% throughout the development of human fetus. In chick the percentage was fairly high(6.7%) during the embryonic stage but began to a gradual decrease at 3 days before hatching and continued to decrease after the hatching until about-10-day old. On the other hand, in rat the percentage was low(2.0%) during the embryonic stage and gradually increased after birth until 15-day old.
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