Itraconazole内用液の単回および反復投与における薬物動態

• 丁 宗鉄

  北里研究所臨床薬理研究所北里研究所バイオイアトリックセンター

• 山本 慧

  北里研究所臨床薬理研究所北里研究所バイオイアトリックセンター

• 井上 晃一

  ヤンセンファーマ株式会社臨床薬理部

• 鳥居 慎一

  ヤンセンファーマ株式会社臨床薬理部

書誌事項

タイトル別名

• Single-and multiple-dose pharmacokinetics of Itraconazole oral solution in healthy men

抄録

Itraconazole (ITCZ) has broad-spectrum antifungal activity, and ITCZ capsules have already been used for systemic and superficial fungal infections. A new formulation of ITCZ, an oral solution, has recently been developed. ITCZ is combined with hydroxypropyl-β-cyclodextrin (HP-β-CD), a vehicle that improves the solubility of ITCZ.<BR>The pharmacokinetics of the ITCZ oral solution were examined both in single and repeated administration in healthy men. The effect of food intake in the single administration of ITCZ oral solution 100mg was evaluated when ITCZ oral solution was administered under fasting or under fed conditions. The Cmax of the fasting group is 1.7-fold higher than the fed group, and the area under the plasma concentration-time curve from time zero to infinity (AUC_0→∞) of the fasting group is 1.1-fold higher than the fed group. In single administration studies of ITCZ oral solution of 100, 200, 300, and 400mg under fasting condition, Cmax and AUC_0→∞ of ITCZ and hydroxy-itraconazole (OH-ITCZ: active metabolite) increased dose-dependently and there was no difference between dosage groups both in the time to reach Cmax (Tmax) and the terminal half-life (t_1/2). In repeated administration studies, no significant drug accumulation was observed. The trough plasma concentration of ITCZ and OH-ITCZ in repeated administration of ITCZ oral solution 100mg stabilized by day 9, and in repeated administration of 200mg, stabilization is reached by day 12. With ITCZ oral solution, mild softened feces are observed, but they are probably due to the side effect of HP-β-CD. ITCZ oral solution is well tolerated by healthy men. From the results, it is also clear that the plasma concentration of ITCZ increased faster and Cmax is higher with ITCZ oral solution than capsules, and the absorption of ITCZ oral solution is regular.

収録刊行物

• 日本化学療法学会雑誌

  日本化学療法学会雑誌 54 (Supplement1), 6-17, 2006

  公益社団法人 日本化学療法学会

キーワード

• itraconazole
• oral solution
• pharmacokinetics
• hydroxypropyl-β-cyclodextrin

詳細情報

• CRID: 1390001206290571904
• NII論文ID: 10018303662
• NII論文ID: 130004298315
• NII書誌ID: AN10472127
• DOI: 10.11250/chemotherapy1995.54.supplement1_6
• ISSN: 18845886
• ISSN: 13407007
• Web Site: https://search.jamas.or.jp/link/ui/2007049429
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
  • Crossref
• 抄録ライセンスフラグ: 使用不可