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

SUGIYAMA Masatoshi, OKAMURA Kentarou, GOTO Mitsuyoshi, KITANO Morihisa

doi:10.3164/jcbn.1.171

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.

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

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