Human studies with "high dose" metronidazole: a non-toxic radiosensitizer of hypoxic cells

Abstract

The serum concentrations of the radiosensitizer metronidazole have been determined in mice for both oral and intraperitoneal doses of the drug and these have been related to radiosensitization studies in murine tumour systems. In preliminary work before a possible clinical trail the serum metronidazole concentration/time curves have been determined in 7 patients using single doses of metronidazole of up to 15 g. The data suggest that a linear relationship exists between the metronidazole dose expressed in mg/kg and the peak serum concentration. The possibility of achieving radiosensitization of tumours in patients after tolerable doses of metronidazole is discussed in relation to enhancement ratios determined for in vitro and in vivo systems. It is concluded that predictions from in vitro systems give values that are probably too optimistic.