Cossu F, Rombi G P, Mazza S, Facchini A
Int J Clin Pharmacol Res. 1986;6(4):317-23.
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.
在先前的细胞培养研究中，作者已证明替硝唑对缺氧细胞具有放射增敏特性，类似于甲硝唑。替硝唑在体外使用1毫摩尔浓度时具有放射增敏活性。本研究的目的是确定在接受放射治疗的患者中产生有效放射增敏作用所需的替硝唑剂量。通过每天给患者使用1.5克、3克、4.5克该药物连续两天单剂量给药，研究替硝唑的药代动力学特性。在48小时内通过15组样本测定血浆浓度。此外，使用高压液相色谱技术在一组患者中研究了替硝唑的肿瘤内浓度。结果表明，4.5克替硝唑的剂量足以达到与体外产生放射增敏作用相似的血浆和肿瘤内浓度，增强因子比约为1.5。还确定了初始剂量和蓄积因子，以便将上述浓度维持足够长的时间，从而能够应用每日多次分割放疗。在整个研究过程中该药物的耐受性良好。
