@article {Nakase382, author = {Yuen Nakase and Akeo Hagiwara and Syuichi Kin and Ken-ichirou Fukuda and Tadao Ito and Tsuyoshi Takagi and Jyunshin Fujiyama and Chohei Sakakura and Eigo Otsuji and Hisakazu Yamagishi}, title = {Intratumoral Administration of Methotrexate Bound to Activated Carbon Particles: Antitumor Effectiveness against Human Colon Carcinoma Xenografts and Acute Toxicity in Mice}, volume = {311}, number = {1}, pages = {382--387}, year = {2004}, doi = {10.1124/jpet.104.069450}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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 LD50 values 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. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/311/1/382}, eprint = {https://jpet.aspetjournals.org/content/311/1/382.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }