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美司钠在体外可使铂类药物失活。

Mesna inactivates platinum agents in vitro.

作者信息

Wolff J E, Egeler R M, Anderson R, Ujack E, Iceton S, Coppes M J

机构信息

Alberta Children's Hospital, Calgary, Canada.

出版信息

Anticancer Res. 1998 Nov-Dec;18(6A):4077-81.

PMID:9891448
Abstract

BACKGROUND

Platinum agents are frequently combined with ifosfamide. Mesna, originally coadministered to protect from ifosfamide side effects, might also react with the platinum agents in these combinations.

METHODS

Malignant glioma cells were incubated with cisplatin, carboplatin and mesna. Cell numbers were measured by counting and by MTT-tests.

RESULTS

In cell free solution mesna turned MTT to its blue farmazan product. Mesna's effect on cells were cell-line specific: It penetrated U87 cells without effect on growth, reduced cell numbers in C6 and T98G cells and did not alter U251 cells. The concentration of cisplatin killing 50% of the cells were 7 x 10(-7) in C6, 9.7 x 10(-6) in T98G, 1.2 x 10(-5) in U251 and 2.4 x 10(-4) in U87 cells. For the same effect, carboplatin required 3-10 times higher concentrations. Mesna protected all cell lines from the cytotoxicity of the platinum agents.

CONCLUSION

Clinical studies should specify in detail, infusion schedules of mesna and platinum agents.

摘要

背景

铂类药物常与异环磷酰胺联合使用。美司钠最初用于预防异环磷酰胺的副作用,但在这些联合用药中也可能与铂类药物发生反应。

方法

将恶性胶质瘤细胞与顺铂、卡铂和美司钠一起孵育。通过计数和MTT试验测量细胞数量。

结果

在无细胞溶液中,美司钠将MTT转化为其蓝色甲臜产物。美司钠对细胞的作用具有细胞系特异性:它可穿透U87细胞且对其生长无影响,减少C6和T98G细胞的数量,而对U251细胞无影响。在C6细胞中,杀死50%细胞的顺铂浓度为7×10⁻⁷,在T98G细胞中为9.7×10⁻⁶,在U251细胞中为1.2×10⁻⁵,在U87细胞中为2.4×10⁻⁴。对于相同的效果,卡铂所需浓度高3至10倍。美司钠可保护所有细胞系免受铂类药物的细胞毒性。

结论

临床研究应详细说明美司钠和铂类药物的输注方案。

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引用本文的文献

1
Influence of mesna on the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.美司钠对小儿癌症患者顺铂和卡铂药代动力学的影响。
Med Oncol. 2004;21(1):9-20. doi: 10.1385/MO:21:1:09.
2
Clinical pharmacokinetics and pharmacodynamics of ifosfamide and its metabolites.异环磷酰胺及其代谢产物的临床药代动力学和药效学
Clin Pharmacokinet. 2001 Jan;40(1):41-62. doi: 10.2165/00003088-200140010-00004.