Rojanasthien N, Kumsorn B, Atikachai B, Leotrakul S, Thongprasert S
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Thailand.
Int J Clin Pharmacol Ther. 2001 Mar;39(3):121-5. doi: 10.5414/cpp39121.
SUBJECTS, MATERIAL AND METHODS: Protective effects of fosfomycin on cisplatin-induced nephrotoxicity have been previously reported, however, the proper time, duration and dosage of its administration were uncertain. Therefore, we investigated the protective effect of concurrent administration of twice-daily doses of 2 g fosfomycin for 5 days in 13 cisplatin-naïve lung cancer patients who were due to receive a single dose per cycle of 100 mg/m2 cisplatin. On each chemotherapeutic cycle, patients were randomly given cisplatin alone or cisplatin plus fosfomycin every 4 weeks for a maximum of 4 consecutive cycles. Indicators of nephrotoxicity, urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, serum creatinine (Scr) and creatinine clearance (Clcr) were determined the day before and at day 3 and day 6 after cisplatin administration. Results were compared and statistically analyzed by the non-parametric Mann-Whitney's test. We found that the NAG activities obtained on day 0, day 3 and day 6 of the fosfomycin cycles were comparable to values obtained during the control cycles (p > 0.05). Moreover, the NAG activities on day 3 of both treatment cycles were significantly elevated from baseline (p < 0.01) and had normalized on day 6. There were no significant changes in serum creatinine and creatinine clearance.
High-dose cisplatin induced reversible elevation of urinary NAG and concurrent administration of low-dose fosfomycin for 5 days had no effect on the enzymuria. In the prevention of cisplatin nephrotoxicity, a further study using dose escalation (8 to 12 g/d) of fosfomycin administered 2 to 3 days prior to cisplatin are required to demonstrate its nephroprotective effects.
研究对象、材料与方法：先前已有关于磷霉素对顺铂诱导的肾毒性的保护作用的报道，然而，其给药的合适时间、持续时间和剂量尚不确定。因此，我们在13例初治的肺癌患者中进行了研究，这些患者每周期接受100mg/m²顺铂单剂量治疗，研究每日两次给予2g磷霉素共5天的同时给药的保护作用。在每个化疗周期，患者每4周随机单独给予顺铂或顺铂加磷霉素，最多连续进行4个周期。在顺铂给药前一天以及给药后第3天和第6天测定肾毒性指标、尿N - 乙酰 - β - D - 氨基葡萄糖苷酶（NAG）活性、血清肌酐（Scr）和肌酐清除率（Clcr）。结果通过非参数曼 - 惠特尼检验进行比较和统计学分析。我们发现，在磷霉素治疗周期的第0天、第3天和第6天获得的NAG活性与对照周期获得的值相当（p>0.05）。此外，两个治疗周期第3天的NAG活性均较基线显著升高（p<0.01），并在第6天恢复正常。血清肌酐和肌酐清除率无显著变化。
高剂量顺铂诱导尿NAG可逆性升高，同时给予低剂量磷霉素5天对酶尿无影响。在预防顺铂肾毒性方面，需要进一步研究在顺铂给药前2至3天使用递增剂量（8至12g/d）的磷霉素以证明其肾保护作用。
