Misonidazole and Desmethylmisonidazole in Clinical Radiotherapy
The first administration of misonidazole to a patient receiving radiotherapy was performed at Mount Vernon on the 1st November 1974. In the first phase of the work, when large single doses were given to 8 patients, we showed that good serum concentrations could be achieved in man with doses which were fairly well tolerated when given orally. The curve of plasma concentration showed a peak at 1 to 2 hours and then a period of slow-fall called the plateau period extending up to 4 or 5 hours. The concentration then fell away with a half-life of approximately 12 hours. Enhancement of radiation response in skin made artificially hypoxic was demonstrated in all 6 cases studied and concentrations up to 100% of the plasma concentration were found in biopsies of human tumours. An enhancement of tumour response was observed in 3 of 4 patients with multiple deposits of tumour where a comparison could be made of treatment with or without the drug (1,2,3).
KeywordsHyperbaric Oxygen Hypoxic Cell Hypoxic Tumour Cell Tumour Concentration Plateau Concentration
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