Ethanol-Moxalactam Interactions in Vivo

Buening, Mildred K.; Wold, J. S.

doi:10.1093/clinids/4.supplement_3.s555

Cited by 30 publications

(13 citation statements)

References 20 publications

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“…These com pounds specifically inhibit hepatic aldehyde dehydrogenase (EC 1.2.1.3, ALDH), which is an enzyme primarily involved in the metabolism of ethanol-derived acetal dehyde to acetic acid (2). Recently, several beta-lactam antibiotics, having an N methyltetrazolylthiomethyl group at the 3 position of the cephem nucleus, were re ported to display a reaction similar to that of disulfiram (3)(4)(5)(6). Subsequent studies showed that hepatic low Km ALDH activity was depressed markedly by the administration of ** To whom reprint requests should be addressed .…”

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Effects of alcohol-metabolizing enzyme inhibitors and beta-lactam antibiotics on ethanol elimination in rats.

et al. 1987

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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.

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Effects of alcohol-metabolizing enzyme inhibitors and beta-lactam antibiotics on ethanol elimination in rats.

et al. 1987

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“…NMTT is a common 3'-position substi tuent of the cephalosporin nucleus of beta lactam antibiotics, which display a disul firam-like reaction (2)(3)(4)(5)(6)(7)(8)(9)(10)21). Adminis tration of NMTT resulted in a rapid onset of the disulfiram-like reaction in rats (Figs.…”

Section: Methodsmentioning

confidence: 99%

“…Buening et al (3,4) and Yanagihara et al (7,8) (9,10). Thus, these antibiotics are supposed to depress the low Km ALDH activity in liver mitochondria followed by an increase in the blood acetaldehyde level during ethanol metabolism (10).…”

Section: Severalmentioning

confidence: 99%

Effects of beta-lactam antibiotics and N-methyltetrazolethiol on the alcohol-metabolizing system in rats.

et al. 1987

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Abstract-The disulfiram-like effect of various beta-lactam antibiotics containing N-methyltetrazolethiol (NMTT) on the alcohol-metabolizing system was studied using rats. Their administration caused decreased activities in low Km aldehyde dehydrogenase (ALDH) and acetaldehyde oxidation in the liver, with marked depression from several hours to 2 days after the treatment.Blood acetaldehyde level increased markedly when ethanol was administered 18-24 hr after pretreat ment with antibiotics.A similar time course change in the effect was obtained when disulfiram was administered.The following results obtained in the present study indicate that the disulfiram-like effect associated with these antibiotics was not mediated by the whole molecular structures of these drugs: Firstly, the antibiotics were eliminated rapidly from the plasma and liver, and the disulfiram like effect was followed by a disappearance of the drugs. Secondly, the concen tration of antibiotics required to inhibit mitochondrial low Km ALDH activity in vitro was very high compared with their liver concentration.Thirdly, rapid onset of disulfiram-like effects occurred after administration of NMTT itself, and a pronounced elevation of blood acetaldehyde level was observed when ethanol was administered 3-5 hr after the NMTT injection. Fourthly, almost the same amounts of NMTT were released in the body after the intravenous administration of various NMTT-containing antibiotics, as judged by the urinary excretion. These results suggest that the disulfiram-like effect of beta-lactam antibiotics is mediated by NMTT released from them.

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“…Like disulfiram, several beta-lactam an tibiotics, having an N-methyltetrazolylthio methyl group at the 3-position of the cepha losporin nucleus, increase blood acetal dehyde level when animals pretreated with these antibiotics were given ethanol (1)(2)(3). Subsequent studies demonstrated the de pression of hepatic low Km aldehyde de hydrogenase (ALDH) activity following the administration of these antibiotics (4-6).…”

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Effects of beta-lactam antibiotics on the acetaldehyde-metabolizing system in germ-free rats.

et al. 1987

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Ethanol-Moxalactam Interactions in Vivo

Cited by 30 publications

References 20 publications

Effects of alcohol-metabolizing enzyme inhibitors and beta-lactam antibiotics on ethanol elimination in rats.

Effects of alcohol-metabolizing enzyme inhibitors and beta-lactam antibiotics on ethanol elimination in rats.

Effects of beta-lactam antibiotics and N-methyltetrazolethiol on the alcohol-metabolizing system in rats.

Effects of beta-lactam antibiotics on the acetaldehyde-metabolizing system in germ-free rats.

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