Characterization of metronidazole-phosphate, a water-soluble metronidazole derivative, as a radiosensitizer of hypoxic cells.
A water-soluble derivative of metronidazole (Flagyl) was synthetized with the purpose to overcome some practical difficulties in the clinical administration of the drug. The derivative, a phosphate ester of metronidazole, was characterized for different physical-chemical properties. It had a low toxicity both in vitro and in vivo. In vitro, it retained a radiosensitizing effect specific for hypoxic cells which was, however, decreased in comparison with the parent compound. The decreased sensitization was related to a decreased one-electron reduction potential and octanol/water partition coefficient. In mice, metronidazole-phosphate had a prolonged blood life in comparison to metronidazole.
D000818:Animals; D006224:Cricetinae; D004583:Electrons; D006207:Half-Life; D000860:Hypoxia; D008297:Male; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D010101:Oxygen Consumption / Q000528:radiation effects; D012995:Solubility; D013997:Time Factors; D014867:Water
D014867:Water; D008795:Metronidazole