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  • Title: Radiosensitization by tinidazole: pharmacokinetic study.
    Author: Cossu F, Rombi GP, Mazza S, Facchini A.
    Journal: Int J Clin Pharmacol Res; 1986; 6(4):317-23. PubMed ID: 3759284.
    Abstract:
    In previous study on cell-cultures, the authors have proved that tinidazole had radiosensitizing properties on hypoxic cells similar to those of metronidazole. The radiosensitizing activity of tinidazole becomes useful in vitro using a concentration of 1 millimol. The purpose of this study was to determine the dose of tinidazole necessary to produce a useful radiosensitizing effect in patients cured by radiotherapy. The pharmacokinetic properties of tinidazole were studied by treating patients with 1.5-3-4.5 g of the drug per day, using single doses for two consecutive days. The plasma concentration was determined by 15 series samples during a period of 48 h. Moreover endotumoural concentrations of tinidazole were studied in a group of patients using high pressure liquid chromatography techniques. The results showed that a dose of 4.5 g of tinidazole was sufficient to reach plasmatic and endotumoural concentrations similar to those which provide a radiosensitizing effect in vitro with an enhancement factor ratio of approximately 1.5. The initial dose and the accumulation factor were also determined in order to maintain the above-mentioned concentrations for a time sufficient to be able to apply multiple daily fractions of radiotherapy. The tolerance of the drug throughout the study was excellent.
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