Effects of ethanol ingestion on the metabolism of a hepatotoxic dose of paracetamol in mice.
Effects of ethanol ingestion on the metabolism of a hepatotoxic dose of paracetamol in mice.
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乙醇摄入对小鼠肝毒性剂量的扑热息痛代谢的影响。
DOI：
10.3109/00498258609043556
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
R. Williams
中科院分区：
文献类型：
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作者：
J. Tredger;H. Smith;R. B. Read;R. Williams
给小鼠给予肝毒性剂量的扑热息痛（400 mg/kg体重，p.o.）后，药物及其葡糖苷在一小时内的峰值血浆浓度约为900微米。相应水平的硫酸盐、巯基和半胱氨酸缀合物分别约为100、35和20微米。给药31 h后尿排泄占给药量的55%。其中对乙酰氨基酚葡萄糖醛酸酯占64.7%，对乙酰氨基酚半胱氨酸占17.9%，硫酸对乙酰氨基酚占10.4%，巯基对乙酰氨基酚占0.5%，不变药占6.5%。急性乙醇给药（3 g/kg, p.o.，与扑热息痛同时给药）1小时后，血浆中葡萄糖醛酸盐、半胱氨酸和巯基酸缀合物的水平下降了约50%。尿中葡萄糖醛酸盐（-13%）和半胱氨酸缀合物（-24%）的排泄量减少，但汞酸盐（+52%）、硫酸盐（+ 11%）和不变药物（+81%）的量增加。慢性乙醇摄入（15 g/kg / d，持续28 d）引起血浆对乙酰氨基酚半胱氨酸（+32%）和巯基糖酸盐（+41%）浓度的短暂初始增加，但尿排泄的唯一实质性变化是对乙酰氨基酚葡萄糖醛酸盐的量增加29%。慢性乙醇消耗后，急性乙醇给药对扑热息痛单氧氧化有短暂的抑制作用，但葡萄糖醛酸化不受影响（根据血浆浓度判断）。只有对乙酰氨基酚汞的排泄受到明显影响（+64%）。
After administration to mice of a hepatotoxic dose of paracetamol (400 mg/kg body wt, p.o.) peak plasma concentrations of the drug and its glucuronide were approximately 900 microM around one hour. Corresponding levels of the sulphate, mercapturate and cysteine conjugates were approximately 100, 35 and 20 microM, respectively. Urinary excretion accounted for 55% of the administered drug 31 h after dosing. Of this total, 64.7% was paracetamol glucuronide, 17.9% paracetamol cysteine, 10.4% paracetamol sulphate, 0.5% paracetamol mercapturate and 6.5% unchanged drug. One hour after acute ethanol administration (3 g/kg, p.o., concomitantly with paracetamol) plasma levels of the glucuronide, cysteine and mercapturate conjugates were decreased by approximately 50%. There were reductions in the urinary excretion of the glucuronide (-13%) and cysteine conjugates (-24%), but increases in the amounts of mercapturate (+52%), sulphate +11%) and unchanged drug (+81%). Chronic ethanol ingestion (15 g/kg per d for 28 d) caused a transient initial increase in plasma paracetamol cysteine (+32%) and mercapturate (+41%) concentrations, but the only substantial change in urinary excretion was a 29% increase in the amount of paracetamol glucuronide. After chronic ethanol consumption, acute ethanol administration had a transient inhibitory effect on paracetamol mono-oxygenation, but glucuronidation was unaffected (as judged by plasma concentrations). Only paracetamol mercapturate excretion was substantially affected (+64%).
长期喂食乙醇的大鼠胆汁排泄对乙酰氨基酚的改变。
DOI：
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发表时间：
1984
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
Vendemiale,G;Altomare,E;Lieber,CS
通讯作者：
Lieber,CS
通过对大鼠进行急性乙醇注射来预防对乙酰氨基酚诱导的肝毒性：与四氯化碳诱导的肝毒性的比较。
DOI：
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发表时间：
1981
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Sato,C;Nakano,M;Lieber,CS
通讯作者：
Lieber,CS
乙醇对对乙酰氨基酚引起的肝毒性的预防作用机制。
DOI：
--
发表时间：
1981
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Sato,C;Lieber,CS
通讯作者：
Lieber,CS