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  • 标题:Decreased Cyclosporin A Concentrations in the Absorption Phase Using Microemulsion Preconcentrate Formulation in Rats with Cisplatin-Induced Acute Renal Failure
  • 本地全文:下载
  • 作者:Toshiaki Igarashi ; Ikuko Yano ; Hideyuki Saito
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2003
  • 卷号:26
  • 期号:11
  • 页码:1591-1595
  • DOI:10.1248/bpb.26.1591
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    Cyclosporin A pharmacokinetics was studied in rats with cisplatin-induced acute renal failure (ARF) using microemulsion preconcentrate (MEPC) and completely dissolved formulations. Although the pharmacokinetics of cyclosporin A was unchanged after intravenous administration, maximum concentration of cyclosporin A in ARF rats was significantly reduced to 608±62 and 999±189 ng/ml compared with 1720±142 and 1832±250 ng/ml in controls after oral administration of MEPC and completely dissolved formulations, respectively. In an in situ intestinal loop sac study, the amount absorbed plus metabolized and the blood concentration of cyclosporin A were similar between control and ARF rats, and taurocholic acid, one of the bile acids, significantly increased absorption of cyclosporin A using the MEPC formulation in both control and ARF rats; the amount absorbed plus metabolized with taurocholic acid was increased to 137 and 186%, and simultaneously the blood concentration was increased to 155 and 158% of that without taurocholic acid in control and ARF rats, respectively. The bile flow in ARF rats was decreased compared with that in controls. These results suggested that renal dysfunction decreased the absorption of cyclosporin A in spite of the MEPC formulation, and the alternation of bile secretion partly affected the absorption rate of cyclosporin A in the gastrointestinal tract.

  • 关键词:cyclosporin A; pharmacokinetics; acute renal failure; microemulsion preconcentrate (MEPC) formulation
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