Dragovic J, Kim S H, Brown S L, Kim J H
Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI 48202, USA.
Radiother Oncol. 1995 Sep;36(3):225-8. doi: 10.1016/0167-8140(95)01581-z.
Pharmacokinetic analyses were performed on blood samples of 12 patients undergoing treatment with nicotinamide, hyperthermia and radiation therapy for a variety of recurrent/metastatic cancers. Escalating oral doses of 3, 4, 5, 6 and 10 g of nicotinamide showed a linear relationship between maximum recorded plasma concentrations and the dose in grams (correlation coefficient, r = 0.91). Maximum plasma levels were observed by 30 min in most patients ingesting up to 6 g of nicotinamide. In marked contrast, five out of six patients ingesting 10 g of nicotinamide demonstrated increasing plasma levels at least up to 3 h post-ingestion. Doses up to 6 g were well tolerated and resulted in average maximum recorded plasma levels (mean +/- 1 SEM) of 156.4 +/- 33.6 micrograms/ml. Doses of 10 g were generally not well tolerated, but a high plasma level was maintained on average for at least 4 h. Plasma concentrations of the above order have been previously associated with maximal enhancement of radiation damage in mouse tumor models. This suggests that radiosensitization can be expected to occur in human tumors following oral administration of a safe and well tolerated dose of 6 g. However, at higher doses (i.e., 10 g), the pharmacokinetics, and perhaps radiosensitization, may differ markedly.
对12例接受烟酰胺、热疗和放射治疗的复发性/转移性癌症患者的血样进行了药代动力学分析。递增口服剂量为3、4、5、6和10克烟酰胺，结果显示最大记录血浆浓度与克剂量之间呈线性关系（相关系数，r = 0.91）。大多数摄入6克以下烟酰胺的患者在30分钟时观察到血浆浓度达到最高水平。与之形成显著对比的是，摄入10克烟酰胺的6例患者中有5例在摄入后至少3小时内血浆浓度持续升高。6克以下的剂量耐受性良好，平均最大记录血浆浓度（均值±1标准误）为156.4±33.6微克/毫升。10克的剂量通常耐受性不佳，但平均至少能维持4小时的高血浆浓度。上述血浆浓度水平此前已在小鼠肿瘤模型中与辐射损伤的最大增强相关联。这表明口服6克安全且耐受性良好的剂量后，有望在人类肿瘤中产生放射增敏作用。然而，在更高剂量（即10克）时，药代动力学以及或许放射增敏作用可能会有显著差异。
