对乙酰氨基酚及其N-乙酰-DL-蛋氨酸酯（SUR 2647组合）同时给药的毒性作用的体内研究。

In vivo studies on toxic effects of concurrent administration of paracetamol and its N-acetyl-DL-methionine ester (SUR 2647 combination).

Skoglund L A, Ingebrigtsen K, Nafstad I, Aalen O

Department of Pharmacology and Toxicology, Norwegian College of Veterinary Medicine, Oslo.

Gen Pharmacol. 1988;19(2):213-7. doi: 10.1016/0306-3623(88)90063-8.

Abstract

Single p.o. doses of paracetamol 400 and 800 mg/kg or SUR 2647 combination (free paracetamol + paracetamol-N-acetyl-DL-methionate, paracetamol/methionine ratio 2:1) equivalent to paracetamol 400 and 800 mg/kg were given to Bom:NMRI mice. Vehicle treated (1% w/v aqueous methylcellulose) mice were established as a control group. 2. All treatment groups irrespective of medication caused an initial GSH depletion. However, SUR 2647 combination 400 mg/kg caused a much earlier hepatic GSH recovery than paracetamol 400 mg/kg. SUR 2647 combination 800 mg/kg caused a higher hepatic GSH level than paracetamol 800 mg/kg. 3. There was no significant difference in the plasma ALAT level after SUR 2647 combination 400 or 800 mg/kg and the control group. Paracetamol 400 and 800 mg/kg caused significant plasma ALAT elevations compared to the control group. 4. The addition of N-acetyl-DL-methionine esterified to paracetamol, as in the SUR 2647 combination, enhances the hepatic GSH synthesizing capacity in Bom:NMRI mice after experimental overdosage and offers protection of hepatic cell integrity as assessed by plasma ALAT level compared to paracetamol alone.

摘要

给Bom:NMRI小鼠口服单剂量对乙酰氨基酚400和800 mg/kg，或与SUR 2647联合用药（游离对乙酰氨基酚+对乙酰氨基酚-N-乙酰-DL-蛋氨酸，对乙酰氨基酚/蛋氨酸比例为2:1），剂量分别相当于对乙酰氨基酚400和800 mg/kg。以经赋形剂处理（1% w/v甲基纤维素水溶液）的小鼠作为对照组。2. 所有治疗组，无论使用何种药物，最初均导致谷胱甘肽（GSH）耗竭。然而，400 mg/kg的SUR 2647联合用药组比400 mg/kg对乙酰氨基酚组的肝脏GSH恢复要早得多。800 mg/kg的SUR 2647联合用药组的肝脏GSH水平高于800 mg/kg对乙酰氨基酚组。3. 400或800 mg/kg的SUR 2647联合用药组与对照组相比，血浆丙氨酸转氨酶（ALAT）水平无显著差异。与对照组相比，400和800 mg/kg对乙酰氨基酚组导致血浆ALAT显著升高。4. 如SUR 2647联合用药那样，将N-乙酰-DL-蛋氨酸与对乙酰氨基酚酯化后添加，可增强实验性过量用药后Bom:NMRI小鼠的肝脏GSH合成能力，并与单独使用对乙酰氨基酚相比，根据血浆ALAT水平评估，对肝细胞完整性具有保护作用。