The clinical testing of Ro 03-8799--pharmacokinetics, toxicology, tissue and tumor concentrations.
Ro 03-8799, a lipophilic nitroimidazole with a basic side chain, has now been administered intravenously to 69 patients. The elimination half-life in plasma was 5.1 hr and the plasma concentration at 30 min was 14.8 micrograms/ml standardized to a dose of 1 g per square meter of surface area. Immediate symptoms of malaise, heat, sweating and disorientation limit the amount of the drug which may be given on any one occasion. However, a dose of 750 mg per square meter of surface area may be given combined with daily radiotherapy. Our data suggest that when given with a 20 fraction course of radiotherapy, sensitization of hypoxic cells may be achieved equal to a 10-fold increase in the dose of misonidazole above that presently permitted.
D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000378:metabolism*; D009593:Nitroimidazoles / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D013997:Time Factors; D014018:Tissue Distribution
D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C033815:pimonidazole