AUC-Dependent Cytotoxicity of Cyclophosphamide against Human Tumors Transplanted into Nude Mice

• SUGIYAMA Masatoshi

  Department of Pharmacy, Fukui Medical School Hospital

• OKAMURA Kentarou

  Department of Pharmacy, Fukui Medical School Hospital

• GOTO Mitsuyoshi

  Department of Pharmacy, Tenri Hospital Present address: Department of Hospital Pharmacy, Nagoya Memorial Hospital

• KITANO Morihisa

  Department of Thoracic Surgery, Tenri Hospital

抄録

We studied the cytotoxicity of cyclophosphamide following the administration of phenobarbital or chloral hydrate to nude mice bearing human tumor xenografts. Cyclophosphamide, 60mg/kg, was injected intraperitoneally once a week for four weeks. The antitumor efficacy of cyclophosphamide was not altered by pretreatment with phenobarbital, but was significantly increased by pretreatment with chloral hydrate. In a parallel study, we measured the concentration of blood NBP-alkylating metabolites in nude mice after administration of cyclophosphamide, 60mg/kg. The AUC (area under blood decay curve) values of NBP-alkylating metabolites were 299±39, 270±13, and 521±57nmol eq nor-mustard ml^-1·h in the controls, phenobarbital-pretreated, and chloral hydrate-pretreated groups, respectively. In contrast, C_max (maximal concentration) values did not show any significant differences among these three groups. An increase in the AUC value of NBP-alkylating metabolites might have led to the stimulation of cytotoxicity of cyclophosphamide in the chloral hydrate-pretreated group. These results indicate that cyclophosphamide possesses AUC-dependent cytotoxicity against human tumor.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｃｌｉｎｉｃａｌ　Ｂｉｏｃｈｅｍｉｓｔｒｙ　ａｎｄ　Ｎｕｔｒｉｔｉｏｎ 1 (2), 171-179, 1986

  一般社団法人　日本酸化ストレス学会

キーワード

• cyclophosphamide
• phenobarbital
• chloral hydrate
• NBP-alkylating metabolites
• AUC

詳細情報

• CRID: 1390282679649495296
• NII論文ID: 130003670167
• DOI: 10.3164/jcbn.1.171
• ISSN: 18805086
• ISSN: 09120009
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可