[Pharmacokinetics and the effects of metronidazole during its use as a radiosensitizer]

During gamma-beam therapy (40-60 Gy) a study was made of the content of metronidazole (MZ) in the blood of 20 patients with oral mucosa cancer and 12 patients with esophageal cancer depending on a mode of its administration. A MZ effect on liver and renal function was studied. MZ was administered to the patients with cancer of both sites on the first 3 days of radiation therapy 3 h before an enlarged fraction of 4 Gy, estimated at 145 mg per 1 kg body mass (8-10 g) per os or via a gastrostoma and 15 g in rectal administration. In the patients with oral mucosa cancer after the administration of MZ per os its level which was sufficient for radiosensitization, was achieved after 2 h and remained for subsequent 4 h with maximum accumulation of 262 +/- 22 micrograms/ml in the blood serum 3-4 h after administration. In 24 h there remained 84 +/- 9 micrograms/ml of MZ in the blood (32% of its maximum level). In the patients with esophageal cancer after MZ administration via the gastrostoma, the nature and time course of drug accumulation in the blood was identical, however accumulation maximum was lower and reached 219 +/- 25 micrograms/ml. In the patients with esophageal cancer after MZ rectal administration, its level in the blood was 118 micrograms/ml only and did not achieve a therapeutically effective level. In repeated administration of MZ per os or via the gastrostoma its accumulation by 25-30% was observed. MZ caused a transient increase in the permeability of the cell membranes of the liver and the suppression of its protein-forming function. It is assumed that the lowering of MZ repeated dose by 20% will cause a decrease in the drug accumulation in the body and the degree of a toxic effect with maintaining its therapeutically effective level in the blood and tumor.