[Metronidazole content of normal and tumor tissues in the combined treatment of patients with osteogenic sarcoma]. / Soderzhanie metronidazola v normal'nykh i opukholevykh tkaniakh pri kombinirovannom lechenii bol'nykh s osteogennoi sarkomoi.

A study was made of the time course of the level of metronidazole in the blood and tissues of 97 patients with localized osteogenic sarcoma in several modes of the drug administration (per os, using an enema and their combinations). The maximum drug concentration in the blood was achieved with the combined mode of the drug administration at a dose of 8 g/m2, enhancing local and general effects on a tumor, manifesting themselves in the reduction of sizes of a tumor, its morphological changes and an increase in the average period of metastasis detection. The 3-year survival rates showed no significant differences between groups of patients receiving and not receiving metronidazole.

[Tissue concentration of methotrexate in osteosarcoma after high-dose infusion].

Tissue concentrations of methotrexate (MTX) in osteosarcomas were examined with special reference to their histologic findings. Primary tumors in five cases and metastatic tumors in two cases were removed at 6-18 days after MTX administration. The concentrations of MTX in osteosarcoma tissues were higher than those in normal tissues and serum, ranging from 15.0 to 168 ng/g. Necrotic portions of the tumor lesion were less in MTX concentration than cellular portions. As the cellularity increased, the tumor tissue showed higher MTX concentration. Tissue concentrations of MTX in nude mice with transplanted osteosarcoma from human were also studied after the high-dose 3H-MTX infusion. MTX total, which contains dihydrofolate reductase-bound MTX, free MTX and its metabolites, decreased gradually with time in the tumor tissues. The concentrations of MTX total in tumor were proportional to the administrated dose and the clearances of MTX were prolonged according to the dose-increase of MTX. Tissue concentrations of MTX total in the lung, kidney and liver were higher than that in tumor itself at 192 hours after the injection. The value for MTX total includes some MTX active fraction which can inhibit the activity of dihydrofolate reductase. Tissue concentrations of MTX active also increased dose-dependently. The proportions of MTX active to MTX total in tumors decreased with the increment of the MTX dose, and the same findings were observed in the kidney and liver.