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Acetaminophen distribution in the rat central nervous system.

机译：对乙酰氨基酚在大鼠中枢神经系统中的分布。

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Based on the evidence that the antinociceptive effects of acetaminophen could be mediated centrally, tissue distribution of the drug after systemic administration was determined in rat anterior and posterior cortex, striatum, hippocampus, hypothalamus, brain stem, ventral and dorsal spinal cord. In a first study, rats were treated with acetaminophen at 100, 200 or 400 mg/kg per os (p.o.), and drug levels were determined at 15, 45, 120, 240 min by high performance liquid chromatography (HPLC) coupled with electrochemical detection (ED). In a second study, 45 min after i.v. administration of [3H]acetaminophen (43 microCi/rat; 0.65 microg/kg), radioactivity was counted in the same structures, plus the septum, the anterior raphe area and the cerebellum. Both methods showed a homogeneous distribution of acetaminophen in all structures studied. Using the HPLC-ED method, maximal distribution appeared at 45 min. Tissue concentrations of acetaminophen then decreased rapidly except at the dose of 400 mg/kg where levels were still high 240 min after administration, probably because of the saturation of clearance mechanisms. Tissue levels increased with the dose up to 200 mg/kg and then leveled off up to 400 mg/kg. Using the radioactive method, it was found that the tissue/blood ratio was remarkably constant throughout the CNS, ranking from 0.39 in the dorsal spinal cord to 0.46 in the cerebellum. These results, indicative of a massive impregnation of all brain regions, are consistent with a central antinociceptive action of acetaminophen.
机译：根据对乙酰氨基酚的镇痛作用可以集中地进行介导的证据，确定了全身给药后大鼠前皮质和后皮质，纹状体，海马，下丘脑，脑干，腹侧和背侧脊髓的组织分布。在第一个研究中，大鼠接受对乙酰氨基酚的口服，口服，口服剂量分别为100、200或400 mg / kg（口服），并通过高效液相色谱（HPLC）和电化学方法在15、45、120、240分钟测定药物水平检测（ED）。在第二项研究中，静脉注射后45分钟给予[3H]对乙酰氨基酚（43 microCi /大鼠; 0.65 microg / kg）时，在相同的结构中加上隔片，前睑裂区和小脑计算出放射性。两种方法均显示对乙酰氨基酚在所有研究的结构中均一分布。使用HPLC-ED方法，最大分布出现在45分钟。然后，对乙酰氨基酚的组织浓度迅速下降，除非剂量为400 mg / kg，给药后240分钟水平仍很高，这可能是由于清除机制饱和所致。组织水平随剂量增加至200 mg / kg而增加，然后趋于稳定至400 mg / kg。使用放射性方法，发现整个CNS的组织/血液比率非常恒定，从背侧脊髓的0.39到小脑的0.46。这些结果表明所有脑区域都大量浸润，这与对乙酰氨基酚的中枢镇痛作用相一致。

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