Phase 1 study of high-dose metronidazole: a specific in vivo and in vitro radiosensitizer of hypoxic cells.
Metronidazole was administered orally to 25 patients and its maximum concentration in blood and tumor tissues, its ability to cross the blood/brain barrier and concentrate in the cerebrospinal fluid and brain tumor tissue, its immediate and long-term toxicity, and its enhancement of irradiation in normal tissue were studied. Maximum blood concentrations of 700-1,200 muM (120-220 mug/ml) were obtained at four hours with doses of 6 g/m2. Moderate and transient nausea and vomiting were the only immediate signs of toxicity. No long-term toxicity was found up to 18 months after administration of the drug. These data indicate that metronidazole can feasibly be adminstered in clinical trials of fractionated radiotherapy using dosages ranging from 9.5 to 11 g three times a week for three to four weeks.
D001932:Brain Neoplasms / Q000532:radiotherapy; D002283:Carcinoma, Bronchogenic / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D006801:Humans; D008175:Lung Neoplasms / Q000532:radiotherapy; D008479:Mediastinal Neoplasms / Q000532:radiotherapy; D008795:Metronidazole / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D009369:Neoplasms / Q000032:analysis / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D011838:Radiation-Sensitizing Agents; D008795:Metronidazole