The in vitro biotransformation of 7-alkoxycoumarin by rat liver microsomes was studied to develop a simple and accurate assay procedure for 7-alkoxycoumarin

No abstract

Abstract-Thein vivo effects of alcohol-metabolizing enzyme inhibitors and beta lactam antibiotics upon the ethanol elimination rate were examined in rats. Intra venous administration of ethanol caused a dose-dependent increase in blood ethanol level, and the ethanol elimination could be well described by a two compart ment model.Pretreatment of rats with enzyme inhibitors caused a marked decrease in the ethanol elimination rate associated with the depression of the enzyme activities. Fasting of the animals caused a decrease in the ethanol elimination rate per animal associated with a decrease in the liver weight.However, no alteration was evident when the rate was expressed as the rate per g of liver. When animals were pre treated with a high dose of N-methyltetrazolethiol (NMTT) containing beta-lactam antibiotics or NMTT itself, which causes a disulfiram-like reaction, the ethanol elimination rate per animal was depressed concomitant with an increase in the blood acetaldehyde level. The ethanol elimination rate in these animals showed lower values even when expressed as the rate per g liver. On the other hand, administration of cephems without NMTT, which cause no disulfiram-like reaction, led to a slight decline in the elimination rate per animal, although no alteration was detected when the rate was expressed as the rate per g liver. The findings indicated that the ethanol elimination in vivo per animal is regulated by the total capacity of the alcohol-metabolizing enzyme activities in the whole liver.

Abstract-Liver microsomal 0-dealkylation activity was determined using 0-methyl, 0-ethyl and 0-propyl derivatives of p-nitrophenol, 7-hydroxycoumarin (umbelliferon) and 7-hydroxyphenoxazone (resorufin) as substrates. Microsomal 0-dealkylation activities of p-nitrophenol and 7-hydroxycoumarin 0-alkyl derivatives were of similar levels, but the activities of 7-hydroxyphenoxazone O-alkyl derivatives were very low compared with those of other substrates. Pretreatment of rats with (9-naphthoflavone resulted in the preferential increase of 0-deethylation and 0-depropylation activities regardless of the ring structure of the substrates, and the ratio of 0-deethylation and 0-depropylation activities to that of 0-demethylation increased markedly. On the other hand, the 0-dealkylase activity of all substrates increased generally upon pretreatment of the rats with phenobarbital, but the ratio of 0-deethylase or 0-depropylase activity to that of 0-demethylase in the pretreated rats was not very different from that of the untreated animals. Hexobarbital inhibited competitively the 0-dealkylation activity in control and phenobarbital-pretreated rat microsomes. On the other hand, the 0-dealkylase activity

Abstract-Effectsof several beta-lactam antibiotics on the acetaldehyde-metabo