Evaluation of the lipid-soluble diaminopyrimidines, metoprine and etoprine, in the avian sarcoma virus rat glioma model.
Using the avian sarcoma virus (ASV) rat glioma model, we have evaluated the in vivo effectiveness of two lipid-soluble folate antagonists, metoprine (DDMP) and its 6-ethyl analog etoprine. When adult Fischer 344 rats, which were previously inoculated with ASV as newborns, received DDMP ip, high levels of this drug accumulated in both normal and gliomatous brain tissue, as well as in lung and liver. When animals bearing ASV-induced gliomas were treated with DDMP or etoprine with or without citrovorum factor (calcium leucovorin), there was no increase in survival, even though the drugs were administered at maximally tolerated doses.
Serano, RD; Sigel, CW; Nichol, CA; Bigner, DD
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