Lockshin A, Giovanella B C, Stehlin J S, Kozielski T, Quian C, Apperson R W
Cancer Res. 1985 Apr;45(4):1797-802.
To avoid infusing large volumes of fluid while treating patients with the standard thymidine solution (30 g/liter), it may be possible to administer this drug in more concentrated form. At 25 degrees C, thymidine is saturating at a concentration of 52 g/liter of 0.6% NaCl solution, and the thymidine concentration at saturation increases with temperature. Nude mice were infused at 29 degrees C with thymidine (60 or 72 g/liter) in cycles consisting of 4 to 5 days infusion followed by 9 days rest. Therapeutically effective doses of concentrated thymidine did not cause significant mortality in mice, and weight loss attributable to treatment was small and reversible. Significant growth inhibition of CA 1 human melanoma heterotransplants was observed after 3 treatment cycles. After 4 or 5 cycles, tumor responses were obtained in 7 mice (6 complete responses) of 12 inoculated with this tumor. These results show that concentrated thymidine solutions are highly effective against human tumor heterotransplants in nude mice and suggest that clinical use of concentrated thymidine may allow practical administration of maximum tolerated doses of this drug.
在使用标准胸苷溶液（30克/升）治疗患者时，为避免输注大量液体，或许可以以更浓缩的形式给药。在25摄氏度时，胸苷在0.6%氯化钠溶液中浓度达到52克/升时达到饱和，且饱和时的胸苷浓度随温度升高而增加。将裸鼠在29摄氏度下以4至5天输注随后9天休息的周期输注胸苷（60或72克/升）。浓缩胸苷的治疗有效剂量在小鼠中未引起显著死亡率，且治疗导致的体重减轻轻微且可逆。在3个治疗周期后观察到CA 1人黑色素瘤异种移植瘤有显著生长抑制。4或5个周期后，接种该肿瘤的12只小鼠中有7只（6只完全缓解）出现肿瘤反应。这些结果表明，浓缩胸苷溶液对裸鼠中的人肿瘤异种移植瘤高度有效，并表明浓缩胸苷的临床应用可能允许实际给予该药物的最大耐受剂量。
