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  • 标题:In Vivo Microdialysis to Determine the Relative Pharmacokinetics of Drugs
  • 本地全文:下载
  • 作者:Mikiro NAKASHIMA ; Mei Feng ZHAO ; Mihoko N. NAKASHIMA
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:1996
  • 卷号:19
  • 期号:7
  • 页码:988-994
  • DOI:10.1248/bpb.19.988
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:The purpose of this study was to evaluate a simultaneous microdialysis method in blood and brain striatum to determine the relative pharmacokinetics and matabolism of L-3, 4-dihydroxyphenylalanine (L-dopa). L-Dopa (250 μmol/kg) was administered to rats with or without the aromatic amino acid decarboxylase (AADC) inhibitor carbidopa (25 μmol/kg) or benserazide (25 or 62.5 μmol/kg). L-Dopa, its metabolites, and AADC inhibitors in dialysates were analyzed by high performance liquid chromatography with an electrochemical detector. A moment analysis was also made to obtain pharmacokinetic parameters.After administration of L-dopa alone, it and its related metabolites were detected in both dialysates of blood and brain striatum. Coadministration of carbidopa (25 μmol/kg) or benserazide (62.5 μmol/kg) significantly enhanced the striatal amount of L-dopa by 8.0 and 6.1 times, respectively. Carbidopa and benserazide also increased striatal amounts of L-dopa metabolites, such as 3, 4-dihydroxyphenylacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol. Inhibition effect of benserazide on an extracerebral decarboxylation of L-dopa to dopamine (DA) was stronger than that of carbidopa. Carbidopa showed a higher striatal level of DA than benserazide. These results suggest a different effect of the two inhibitors on the DA formations in blood and brain striatum, and on the L-dopa transport through the blood-brain barrier (BBB).Thus, microdialysis is an easy and available method for simultaneously assessing the in vivo relative pharmacokinetics and metabolism of drugs in systemic circulation and a target organ.
  • 关键词:brain microdialysis;blood microdialysis;L-3, 4-dihydroxyphenylalanine (L-dopa);inhibitor;drug interaction;pharmacokinetics
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