Field Of Drug Metabolism Research Articles

Highlights of drug metabolism research in China.

In the past 30 years, the study of drug metabolism in China has followed a zigzag path, from the initial uprising stage to devastation, and then to regeneration. In the reviving decade of 1976-1985, studies have extended to various aspects of the field of drug metabolism and pharmacokinetics. There are rapid increases both in modern facilities and trained personnel. Therefore, it is expected that in the coming decade drug metabolism research in China will be carried out at much higher levels with more interesting results.

Cytochrome P-450-Dependent Monooxygenase Activities in Prenatal and Postnatal Human Livers: Comparison of Human Liver 7-Alkoxycoumarin O-Dealkylases with Rat Liver Enzymes

Human liver samples from 17 embryos, 5 fetuses, 5 infants and 4 adults were used to investigate human liver cytochrome P-450-dependent 7-alkoxycoumarin O-dealkylase activities, and their drug-metabolizing activities were compared to those of rat livers. The O-dealkylase activities in human embryos and fetuses were very low, although detectable, similar to those in fetal rats. Both male and female rats showed a postnatal increase of hepatic O-dealkylase activities with a maximum at about 30–40 days after birth and then a decline in the activities which was marked in female rats. Adult female rats showed a marked decrease in the hepatic enzyme activity observed in the O-depropylation reaction rather than the O-demethylation and O-deethylation reactions. During the developmental period of human infants, the O-demethylase activity, but not O-depropylase activity, increased gradually. Enzymes in adult human livers metabolize the O-methyl derivative of 7-hydroxycoumarin in preference to the O-ethyl and O-propyl derivatives. The metabolic activities of human adult enzymes for 7-alkoxycoumarin resembled those in adult female rats and were quite different from those in male rats. The study demonstrated that caution must be exercised in extrapolating pharmacological results from animal to man in the field of drug metabolism.