ABSTRACT
Nimorazole, a 5-Nitromidazole compound has been shown in animal studies to have similar radiosensitizing properties to misonidazole at clinically acceptable dose levels. The drug is well absorbed in humans after oral administration with peak plasma levels occurring around 90 min after ingestion (range 35-135 min) and a plasma half life between 2 and 4.8 hours. Total doses of Nimorazole up to 60 grams given in daily doses with conventional radiation therapy have demonstrated a significant lack of side effects, in particular no demonstrable neurotoxicity.
Subject(s)
Neoplasms/metabolism , Nimorazole/metabolism , Nitroimidazoles/metabolism , Radiation-Sensitizing Agents/metabolism , Adult , Aged , Dose-Response Relationship, Drug , Drug Evaluation , Female , Humans , Male , Middle Aged , Nimorazole/blood , Nimorazole/toxicity , Radiation-Sensitizing Agents/blood , Radiation-Sensitizing Agents/toxicity , Time FactorsABSTRACT
The pharmacokinetics of the hypoxic radio-sensitizer nimorazole were studied in 19 individuals after single oral doses of between 0.5-3.5 g. HPLC measurements showed, after a rapid absorption, a linear relationship between peak plasma concentration and given dose. Mean elimination half life was 3.1 h. A tendency to a dose-dependent variation in the apparent volume of distribution, total body clearance and elimination half life suggest non-linear pharmacokinetics of nimorazole. Tumour concentrations measured in 5 patients gave tumour/plasma ratios between 0.8-1.3. No toxicity was observed. The results indicate that nimorazole may have potential as a clinically useful hypoxic radiosensitizer.
