Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans.
Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans.
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健康人体中 4-甲基吡唑和乙醇之间的动力学相互作用。
DOI：
10.1111/j.1530-0277.1996.tb05255.x
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
McMartin,KE
中科院分区：
文献类型：
--
作者：
Jacobsen,D;Sebastian,CS;Dies,DF;Breau,RL;Spann,EG;Barron,SK;McMartin,KE
4-甲基吡唑（4-Methylpyrazole，4-MP）是一种有效的乙醇脱氢酶活性抑制剂，因其作用时间长、副作用少而成为替代乙醇作为甲醇和乙二醇中毒解毒剂的候选药物。为了研究乙醇和4-MP之间可能的相互抑制作用，采用双盲交叉设计在健康志愿者中进行了两项研究。在研究A中，假定治疗剂量范围为10 - 20 mg/kg的4-MP导致给予0.5 - 0.7 g/kg乙醇的12例受试者的乙醇消除率降低40%。这些数据表明，这种剂量的CMP在体内抑制人体中的醇脱氢酶活性，并且将有效阻断甲醇或乙二醇代谢。在研究B中，乙醇（0.6 g/kg，然后0.2 g/kg，两次）显著降低了4-MP（5 mg/kg，4例受试者静脉给药）的消除速率。这些中等剂量的乙醇还可抑制4-羧基吡唑（人体中4-MP的主要代谢产物）的尿排泄率。数据表明，乙醇抑制4-MP代谢，从而增加体内CMP治疗血液水平的持续时间。这种相互作用可能具有临床意义，因为大多数自我中毒的患者也摄入了乙醇。理论上，甲醇和乙二醇也可能与4-MP发生这种相互作用。
4‐Methylpyrazole (4‐MP), a potent inhibitor of alcohol dehydrogenase activity, is a candidate to replace ethanol as the antidote for methanol and ethylene glycol intoxications, because It has a longer duration of action and apparently fewer adverse effects. To study a probable mutual inhibitory effect between ethanol and 4‐MP on their elimination, two studies were performed in healthy human volunteers using double‐blind crossover designs. In study A, 4‐MP in the presumed therapeutic dose range of 10 to 20 mg/kg caused a 40% reduction in the rate of elimination of ethanol in 12 subjects given 0.5 to 0.7 g/kg of ethanol. These data suggest that such doses of CMP inhibit alcohol dehydrogenase activity in humans in vivo and would be effective at blocking methanol or ethylene glycol metabolism. In study B, ethanol (0.6 g/kg followed by 0.2 g/kg twice) significantly decreased the rate of elimination of 4‐MP (5 mg/kg, given intravenously to four subjects). These moderate doses of ethanol also inhibited the rate of urinary excretion of 4‐carboxypyrazole, the primary metabolite of 4‐MP in humans. Data suggest that ethanol inhibits 4‐MP metabolism, thereby increasing the duration of therapeutic blood levels of CMP in the body. This mutual interaction may have clinical implications, because most self‐poisoned patients have also ingested ethanol. Theoretically, methanol and ethylene glycol might also show such interactions with 4‐MP.