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目的：观察抗癌新药阿托氟啶 (1 Acetyl 3 0 Toluyl 5 FU,ATFU)对人体的毒性，确定耐受剂量，并进行药代动力学研究。方法： 34例肿瘤患者为研究对象，耐受性试验采用改良的 Fibonacci方法，从低剂量逐渐上升至高剂量，每剂量组至少 3例，从给药每日 600 mg开始，连续服用 4周，如无明显毒副反应则进入下一剂量组，直至达到最大耐受量 (MTD)。药代动力学研究采用 HPLC方法，一次性口服 ATFU 800 mg、 1000 mg和 1200 mg，服药后 0～ 26 h定时采集血清标本，测定血清中 ATFU代谢产物的浓度。结果：主要毒副反应是血清谷丙转氨酶 (SGPT)升高， MTD为 1400 mg/d。 ATFU在人体内代谢产物为 TFU，其代谢符合一房室模型特征，三个剂量组的 ATFU药代动力学参数没有显著性差异，平均消除相半衰期分别为 6.35、 7.18和 6.75 h。结论：阿托氟啶对人体毒性可耐受，推荐Ⅱ 期临床用药剂量为单一用药每日 1200 mg，联合化疗每日 800 mg，用药间隔最好为 6 h。
OBJECTIVE: To observe the toxicity of 1-Aetetyl-3-Toluyl-5 FU (ATFU) on humans, determine tolerated doses, and perform pharmacokinetic studies. METHODS: Thirty-four patients with tumors were studied. Tolerability tests were performed using a modified Fibonacci method that gradually increased from low-dose to high-dose, with at least 3 doses per dose, starting at 600 mg daily for 4 weeks. No significant adverse effects were entered in the next dose group until the maximum tolerated dose (MTD) was reached. The pharmacokinetics study was performed by HPLC. One-time oral administration of ATFU 800 mg, 1000 mg, and 1200 mg was performed. Serum samples were taken regularly from 0 to 26 h after administration to determine the concentration of ATFU metabolites in the serum. Results: The main toxicities and side effects were elevation of serum glutamate transaminase (SGPT) with an MTD of 1400 mg/d. The metabolite of ATFU in the human body is TFU, and its metabolism conforms to the characteristics of a one-compartment model. There is no significant difference in the ATFU pharmacokinetic parameters between the three dose groups, and the average elimination half-life is 6.35, 7.18, and 6.75 h, respectively. Conclusion: Atoflumurine is tolerable to humans. It is recommended that the phase II clinical dose be 1200 mg daily for single use and 800 mg daily for combination chemotherapy. The best interval for drug use is 6 h.