| Autor: |
Nakase, Yuen, Hagiwara, Akeo, Kin, Syuichi, Fukuda, Ken-ichirou, Ito, Tadao, Takagi, Tsuyoshi, Fujiyama, Jyunshin, Sakakura, Chohei, Otsuji, Eigo, Yamagishi, Hisakazu |
| Zdroj: |
The Journal of Pharmacology and Experimental Therapeutics; October 2004, Vol. 311 Issue: 1 p382-387, 6p |
| Abstrakt: |
We previously developed a new formulation of methotrexate (MTX) that is adsorbed onto a suspension of activated carbon particles (MTX-CH) and reported the usefulness of local administration in murine tumors. The present study examines the effects of human colon carcinoma (LoVo) xenografts and the acute toxicity of MTX-CH compared with MTX aqueous solution (MTX-AQ) in mice. In therapeutic experiments, LoVo cells were implanted into the backs of BALB/c nude mice. When the cells had developed into tumors, we performed an intratumoral administration of a weekly dose of 30 mg/kg. The MTX concentration in the tumor was compared between the MTX-CH group and MTX-AQ group. In experiments on acute toxicity, MTX-CH and MTX-AQ were injected subcutaneously in BDF1 mice, and intoxication symptoms, changes in body weight, and date of death were recorded. In the therapeutic experiments, intratumoral administration of MTX-CH was much more effective in suppressing the tumor growth compared with MTX-AQ. In experiments of acute toxicity, the death time of the MTX-CH group was delayed to a greater extent, and the 50% lethal dose (LD50) values of MTX-CH were lower than those of MTX-AQ. The LD50values of MTX-CH are 75 times higher than the efficacious dose of 30 mg/kg. The present results suggest that intratumoral administration of MTX-CH is useful for local therapy and the therapeutic dose of MTX-CH can be safely injected subcutaneously. |
| Databáze: |
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