Jacobsen D, Ostensen J, Bredesen L, Ullstein E, McMartin K
Department of Medicine, Ullevaal Hospital, University of Oslo, Norway.
Hum Exp Toxicol. 1996 Jun;15(6):494-6. doi: 10.1177/096032719601500606.
The safety and pharmacokinetics of the alcohol dehydrogenase inhibitor 4-MP have recently been evaluated and its clinical use in ethylene glycol poisoning in France is promising. The dialysability of 4-MP is not known. This is important as hemodialysis is one of the cornerstones in the treatment of (late) ethylene glycol and methanol poisonings. We therefore studied the dialysability of 4-MP in the pig model. Anesthesized pigs (maintained on respirator) given 4-MP, 10 mg/kg, served as controls (n = 3) to the pigs (n = 3) given 15 mg/kg and hemodialyzed for 4 h. 4-MP plasma elimination curves for both groups were compared for 12 h and dialysance data calculated. 4-MP (MW 82) was removed by the same rate as urea (MW 60) by the 0.3 m2 dialysator, thus indicating no significant protein binding of 4-MP. The mean dialysance of 4-MP (and urea) in the three pigs were 61 (63), 51 (53) and 56 (48) ml/min, at a blood flow of 75 ml/min. The amount of 4-MP removed by hemodialysis in 4 h was 57-76 mg compared to a urinary excretion of 1-3 mg over 12 h. We conclude that the dialysability of 4-MP is significant and this must be taken into account when these two treatment procedures are combined.
酒精脱氢酶抑制剂4 - MP的安全性和药代动力学最近已得到评估,其在法国用于乙二醇中毒的临床应用前景广阔。4 - MP的透析性尚不清楚。这一点很重要,因为血液透析是治疗(晚期)乙二醇和甲醇中毒的基石之一。因此,我们在猪模型中研究了4 - MP的透析性。给予10mg/kg 4 - MP的麻醉猪(使用呼吸机维持)作为对照组(n = 3),与给予15mg/kg并进行4小时血液透析的猪(n = 3)进行对比。比较两组猪12小时内的4 - MP血浆消除曲线,并计算透析率数据。0.3平方米的透析器以与尿素(分子量60)相同的速率清除4 - MP(分子量82),这表明4 - MP没有显著的蛋白结合。在血流量为75ml/min时,三只猪中4 - MP(和尿素)的平均透析率分别为61(63)、51(53)和56(48)ml/min。血液透析在4小时内清除的4 - MP量为57 - 76mg,而12小时内尿液排泄量为1 - 3mg。我们得出结论,4 - MP的透析性显著,在联合这两种治疗方法时必须考虑到这一点。