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标题：Pharmacokinetics of Aniracetam and Its Metabolites in Rat Brain
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作者：Taro OGISO ; Kaori UCHIYAMA ; Hiroko SUZUKI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2000
卷号：23
期号：4
页码：482-486
DOI：10.1248/bpb.23.482
出版社：The Pharmaceutical Society of Japan
摘要：The pharmacokinetics of aniracetam (AP) and its main metabolites, 4-p-anisamidobutyric acid (ABA), 2-pyrrolidinone (PD) and p-anisic acid (AA), in 3 brain regions (cerebral cortex, hippocampus and thalamus) was investigated after single intravenous (i.v.) and oral administrations of AP to rats. AP, AA and PD were rapidly distributed into the 3 brain regions after i.v. administration of AP, but the amounts of AP were low. The concentrations of AP and AA in brain regions rapidly declined, whereas PD levels were higher and more sustained than those of AP and AA. ABA levels in the regions were below the detection limit. There were no significant differences in the distribution of these compounds in the 3 brain regions. The AUC_brain/AUC_plasma ratio of PD was 53-55%, in contrast to the low ratio of AP (2.4-3.2%) and AA (3.9-4.2%). On oral administration of AP, the AUC_brain/AUC_plasma ratio of PD was also higher than that of AA. When the transport of PD was tested using the in situ brain perfusion technique, it was clarified that PD was not transported across the blood-brain barrier (BBB) by a neutral amino acid carrier system. The high brain levels of PD and the low levels of AP suggest that the clinical efficacy of dosed AP may partly result from PD penetrating into the brain.
关键词：aniracetam;metabolite;brain pharmacokinetics;brain concentration;brain uptake