Doses Of Misonidazole Research Articles

Biliary and faecal excretion of misonidazole in man.

Although the radiosensitizer misonidazole is now being used widely in clinical trials, much more information is required concerning its metabolism and routes of excretion. This information will be useful in optimizing ways of using the drug in order to reduce peripheral neuropathy, which is its main dose-limiting toxicity, and in the design and development of new drugs structurally related to misonidazole. Flockhart et al. (1978) have investigated urinary excretion in man and shown that only 10–20% of the administered dose of misonidazole is excreted in the urine in the first 24 hours as unchanged drug, plus its o-demethylated metabolite (Ro–05 9963). Less than 1% is excreted as misonidazole glucuronide, while a study using 14C labelling showed that only 2% is excreted as amine derivative.

Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism of reoxygenation.

Abstract The proportion of viable hypoxic cells in EMT6/St/lu tumours assayed 18 and 24 hours after a dose of misonidazole (1.2 mg/g), which killed 80–90% of the tumour cells, was reduced from 20% in the controls to 7% in the misonidazole treated mice. In other experiments, the radiation cell-survival curve of the RIF-1 tumour was assayed in both intradermal and intramuscular sites under both air-breathing and acutely hypoxic conditions. The slope of the survival curve of the intramuscular tumours irradiated under air-breathing conditions was significantly steeper than that of the same tumours growing intradermally (D0 values of 187 rad vs. 357 rad), or when the tumours were irradiated in either site under acutely hypoxic conditions (D0 = 375 rad). Both of these experimental observations are examined in the light of data from other sources, notably from the radiation response of hypoxic cells in spheroids and from observations made from tumours implanted between close, parallel mica sheets (“sandwich” tum...

Relationship between Misonidazole Toxicity and Core Temperature in C3H Mice

A single intraperitoneal injection of the radiation sensitizer misonidazole at doses greater than 0.5 mg/g was found to produce a transient hypothermic response in C3H mice. An increase in the acute toxicity of this drug was demonstrated when the animal core temperature was maintained at a normal 35 to 370C by placing the mice in a warmed environment immediately following injection of the drug. The LDs0/3 day, dose of misonidazole was determined to be 1.48 mg/g for mice allowed to become hypothermic following injection but 0.77 mg/g for mice maintained at a normal core temperature following injection.