Development of an intravenous formulation for the unstable investigational cytotoxic nucleosides 5-azacytosine arabinoside (NSC 281272) and 5-azacytidine (NSC 102816).
Development of an intravenous formulation for the unstable investigational cytotoxic nucleosides 5-azacytosine arabinoside (NSC 281272) and 5-azacytidine (NSC 102816).
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开发不稳定的研究性细胞毒性核苷 5-氮杂胞嘧啶阿糖苷 (NSC 281272) 和 5-氮杂胞苷 (NSC 102816) 的静脉制剂。
DOI：
10.1111/j.2042-7158.1984.tb04860.x
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Repta,AJ
中科院分区：
文献类型：
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作者：
Mojaverian,P;Repta,AJ
在水溶液中，5-氮杂胞嘧啶阿拉伯糖苷（aza-A）（NSC 281272）表现出与5-氮杂胞苷（aza-C）（NSC 102816）类似的复杂和快速降解。因此，它不适合用作缓慢静脉输注。本研究已确定，两种化合物在无水二甲基亚砜（DMSO）或二甲基乙酰胺（DMA）中相对稳定。在水-有机混合溶剂中，随着水含量的降低，降解速率降低。基于这些发现，aza-A可以以100 mg ml−1溶解在DMSO中，无菌过滤，并密封在安瓿中。内容物在4 °C下表现出足够的稳定性，并且可以在使用时用水稀释以产生70% DMSO溶液，其在25 °C下保持>90%效力24小时并且与市售的静脉内输注管相容。可将稀释溶液在线加入流动的静脉注射溶媒中，得到生理学上可接受的溶液，其中药物不稳定（t902 h）。它在到达血液之前的短暂停留时间排除了任何重大损失。
In aqueous solutions 5-azacytosine arabinoside (aza-A) (NSC 281272) exhibits complex and rapid degradation of a type analogous to 5-azacytidine (aza-C) (NSC 102816). Consequently, it is not amenable for use as slow i.v. infusions. This study has determined that both compounds are relatively stable in dry dimethylsulfoxide (DMSO) or dimethylacetamide (DMA). In mixed aqueous-organic solvents, as the water content is reduced the rate of degradation is descreased. Based on these findings, aza-A may be dissolved in DMSO at 100 mg ml−1, sterile filtered, and sealed in ampoules. The contents appear to be adequately stable at 4 °C, and may at the time of use be diluted with water to yield a 70% DMSO solution which retains >90% potency for 24 h at 25 °C and is compatible with commercially available i.v. infusion tubing. The diluted solution may be added in-line to a flowing i.v. vehicle, resulting in a physiologically acceptable solution in which the drug is unstable (t902 h). Its short residence time before reaching the bloodstream precludes any significant loss.