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Following the DAHANCA 5 trial [1], which demonstrated the benefit of the hypoxic radiosensitizer Nimorazole, and the DAHANCA 6&7 trial, which demonstrated that accelerated fractionation added signi...

BACKGROUND: Hypoxia is a characteristic feature of solid tumours that significantly reduces the efficacy of conventional radiation therapy. In this study we investigated the role of hypoxia in a stereotactic radiation schedule by using a variety of hypoxic modifiers in a preclinical tumour model. MATERIAL AND METHODS: C3H mammary carcinomas were irradiated with 3 × 15 Gy during a one-week period, followed three days later by a clamped top-up dose to produce a dose response curve; the endpoint was tumour control. The hypoxic modifiers were nimorazole (200 mg/kg), nicotinamide (120 mg/kg) and carbogen (95% O2 + 5% CO2) breathing, OXi4503 (10 mg/kg), and hyperthermia (41.5°C; 1 h). RESULTS: The radiation dose controlling 50% of clamped tumours (TCD50) following 3 × 15 Gy was 30 Gy. Giving nimorazole or nicotinamide+ carbogen prior to the final 15 Gy fraction non-significantly (χ(2)-test; p < 0.05) reduced this TCD50 to 20-23 Gy; when administered with each 3 × 15 Gy fraction these values were significantly reduced to ≤ 2.5 Gy. Injecting OXi4503 or heating after irradiating significantly reduced the TCD50 to 9-12 Gy regardless of whether administered with one or all three 15 Gy fractions. Combining OXi4503 and heat with the final 15 Gy had a significantly larger effect (TCD50 = 2 Gy). CONCLUSIONS: Clinically relevant modifiers of hypoxia effectively enhanced an equivalent stereotactic radiation treatment confirming the importance of hypoxia in such schedules.

A simple, rapid, sensitive, cost effective, and reproducible chemometrics assisted RP-HPLC method for the simultaneous estimation of the Ofloxacin and Nimorazole in pharmaceutical formulation was developed, optimized, and validated. A chemometrics assisted RP-HPLC method was developed. A developed method was optimized by using central composite design (CCD) in response surface methodology (RSM). Based on the trial and error, percentage of tetrahydrofuran in the mobile phase, flow rate, and buffer molarity were selected as factors. Resolution (Rs2) and retention time (tR2) were used for the estimation of system response during the optimization procedure. Derringer’s desirability function was used to concurrently optimize the selected two responses. Separation was achieved on a Phenomenex C18 column (150 × 4.6 mm i.d, 5µ particle size) with a mobile phase consisting of 25% of Tetrahydrofuran and 75% of Phosphate buffer (25 mM), delivered at a flow rate of 1.2 mL/min with photodiode array detection at 294 nm...

To the Editor, Interaction with vitamin K antagonists can lead to serious adverse reactions [1]. Metronidazole inhibits CYP2C9, which metabolizes vitamin K antagonists [2]. Nimorazole is a 5-nitroi...

CG 10213-Go, a 5-nitroimidazole derivative synthesized at the CIBA-Geigy Research Centre, Bombay, proved superior to such currently used 5-nitroimidazole derivatives as metronidazole, ornidazole, secnidazole, tinidazole and nimorazole, against experimental amoebic infections of the liver and caecum in a golden hamster model. CG 10213-Go is now undergoing clinical trials.