title: Use of ornidazole in fractionated radiotherapy: dose tolerance, serum and tumour tissue concentration.
abstract: Sensitizing and neurotoxic effect of ornidazole, was tested in a double-blind randomized study in patients with carcinoma of the cervix and larynx. Ornidazole or placebo were given orally, two times weekly, for 3 weeks. Dose was 2.5 g/m2 for each administration. Total dose given was 15 g/m2. Radiation therapy was given 3 h after the drug administration. Ornidazole was well tolerated in the majority of the patients. No neurotoxic side effects, such as peripheral neuropathy or convulsion, were observed with a total dose of up to 30 g. Dizziness, somnolence and nausea were the prominent acute side effects, seen mostly (70%) in women. In the placebo group this rate was 17% (p less than 0.01). No important side effect was observed in men receiving ornidazole. Serum concentration of ornidazole reached the maximum level in 2-4 h after oral administration and ranged (23 patients) from 65.1 to 139.8 micrograms/ml. Mean half-life was 15.6 +/- 2.8 h. Peak concentration in tumour tissue was achieved 1-3 h after the administration, ranging from 13.0 to 78.0 micrograms/g. Tumour concentration of ornidazole ranged from 14 to 93% of the serum concentration at the time of irradiation.
mesh_terms: D000328:Adult; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007700:Kinetics; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D009593:Nitroimidazoles / Q000627:therapeutic use*; D009950:Ornidazole / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D011897:Random Allocation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000532:radiotherapy*
chemical_list: D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D009950:Ornidazole