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THE HYPOXIC CELL sensitizer Misonidazole (1 -(2-nitroimidazole1 -yl)-3-methoxypropan-2-ol, MISO) is currently undergoing worldwide trials of its clinical usefulness. Its primary dose-limiting toxicity is peripheral sensory neuropathy (Wasserman et al., 1979) though encephalopathy is occasional. There is no demonstrable dose threshold for these effects, but the total dose has generally been limited to 12 g/m2 (Dische et al., 1977; Urtasun, 1978) in an attempt to reduce the toxicity to acceptable levels. There is evidence that the incidence of neurotoxicity is related to the area under the curve (AUC) of plasma drug concentration against time (Dische et al., 1979) or the "exposure index" as defined by Dische, which is the product of the plasma concentration in the plateau period and the half-life. Potentially, a reduction in AUC or "exposure index" might lead to a lower incidence of neurotoxicity. However, since radiosensitization is dependent upon the tumour concentration of MISO at the time of irradiation (McNally et al., 1978; Brown & Yu, 1980) high plasma levels need to be maintained since these and tumour concentration have been shown to be similar in man (Dische et al., 1979; Ash et al., 1979). It has already been demonstrated that pre-treatment with phenytoin shortens the half-life of MISO in experimental animals (Workman, 1979; White & Workman, 1980) and in patients given 2 large doses of MISO separated by a 14-day course of phenytoin (Workman et al., Accepted 15 June 1981

Phenytoin-induced changes in the pharmacokinetics of misonidazole in radiotherapy patients