内容紹介
Formation of Oxalate in Oxaliplatin Injection Diluted with Infusion Solutions
Summary
Oxaliplatin use can cause acute peripheral neuropathy characterized by sensory paresthesias, which are markedly exacerbated by exposure to cold temperatures, and is a dose-limiting factor in the treatment of colorectal cancer. Oxalate is eliminated in a series of nonenzymatic conversions of oxaliplatin in infusion solutions or biological fluids. Elimination of oxalate from oxaliplatin has been suggested as one of the reasons for the development of acute neuropathy. In this study, we developed a high-performance liquid chromatography(HPLC)-based method to detect oxalate formation, and investigated the time-dependent formation of oxalate in oxaliplatin diluted with infusion solutions. The results obtained showed that the amount of oxalate in the solution corresponded to 1.6% of oxaliplatin 8 h after oxaliplatin dilution with a 5% glucose solution. On the other hand, oxalate formation from oxaliplatin diluted with a saline solution was ten-fold higher than that from oxaliplatin diluted with the 5% glucose solution. Most patients who were intravenously injected with oxaliplatin experienced venous pain. As a preventive measure against venous pain, dexamethasone was added to the oxaliplatin injection. We measured the amount of oxalate formed in the dexamethasone-containing oxaliplatin injection diluted with a 5% glucose solution. The amount of oxalate formed when dexamethasone was added did not differ significantly from that formed when dexamethasone was not added. Thus, there are no clinical problems associated with the stability of oxaliplatin solutions.
要旨
オキサリプラチンは冷感痛覚過敏などを特徴とする急性の末梢神経障害が必発であり,大腸癌治療の規制因子となる。オキサリプラチンは輸液との混合で非酵素的にシュウ酸が脱離するが,シュウ酸は急性の末梢神経障害への関与が示唆されている。今回,輸液中シュウ酸のHPLCによる定量法を開発し,オキサリプラチンと各輸液を混合後,経時的なシュウ酸の生成量を検討した。その結果,5%ブドウ糖液の場合,8時間後のシュウ酸生成量はオキサリプラチンの1.6%であったが,生理食塩液では10倍量のシュウ酸が生成した。また,オキサリプラチンの末梢静脈から投与する際の血管痛対策として,デキサメタゾン注射液をオキサリプラチンに添加する予防法がある。そこで,デキサメタゾン添加によるシュウ酸の生成量を検討した。その結果,デキサメタゾン添加によるシュウ酸の生成量は添加しない場合と有意差はなく,オキサリプラチンの安定性に問題はないと考えられた。
目次
Summary
Oxaliplatin use can cause acute peripheral neuropathy characterized by sensory paresthesias, which are markedly exacerbated by exposure to cold temperatures, and is a dose-limiting factor in the treatment of colorectal cancer. Oxalate is eliminated in a series of nonenzymatic conversions of oxaliplatin in infusion solutions or biological fluids. Elimination of oxalate from oxaliplatin has been suggested as one of the reasons for the development of acute neuropathy. In this study, we developed a high-performance liquid chromatography(HPLC)-based method to detect oxalate formation, and investigated the time-dependent formation of oxalate in oxaliplatin diluted with infusion solutions. The results obtained showed that the amount of oxalate in the solution corresponded to 1.6% of oxaliplatin 8 h after oxaliplatin dilution with a 5% glucose solution. On the other hand, oxalate formation from oxaliplatin diluted with a saline solution was ten-fold higher than that from oxaliplatin diluted with the 5% glucose solution. Most patients who were intravenously injected with oxaliplatin experienced venous pain. As a preventive measure against venous pain, dexamethasone was added to the oxaliplatin injection. We measured the amount of oxalate formed in the dexamethasone-containing oxaliplatin injection diluted with a 5% glucose solution. The amount of oxalate formed when dexamethasone was added did not differ significantly from that formed when dexamethasone was not added. Thus, there are no clinical problems associated with the stability of oxaliplatin solutions.
要旨
オキサリプラチンは冷感痛覚過敏などを特徴とする急性の末梢神経障害が必発であり,大腸癌治療の規制因子となる。オキサリプラチンは輸液との混合で非酵素的にシュウ酸が脱離するが,シュウ酸は急性の末梢神経障害への関与が示唆されている。今回,輸液中シュウ酸のHPLCによる定量法を開発し,オキサリプラチンと各輸液を混合後,経時的なシュウ酸の生成量を検討した。その結果,5%ブドウ糖液の場合,8時間後のシュウ酸生成量はオキサリプラチンの1.6%であったが,生理食塩液では10倍量のシュウ酸が生成した。また,オキサリプラチンの末梢静脈から投与する際の血管痛対策として,デキサメタゾン注射液をオキサリプラチンに添加する予防法がある。そこで,デキサメタゾン添加によるシュウ酸の生成量を検討した。その結果,デキサメタゾン添加によるシュウ酸の生成量は添加しない場合と有意差はなく,オキサリプラチンの安定性に問題はないと考えられた。