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达托霉素与九种药物的物理和化学相容性。

Physical and chemical compatibility of daptomycin with nine medications.

作者信息

Lai Jan-Ji, Brodeur Stephanie K

机构信息

Analytical Chemistry, Cubist Pharmaceuticals, Inc., Lexington, MA, USA.

出版信息

Ann Pharmacother. 2004 Oct;38(10):1612-6. doi: 10.1345/aph.1E124. Epub 2004 Aug 24.

Abstract

BACKGROUND

Hospitalized patients with serious gram-positive infections tend to require concomitant therapy. Unfortunately, a number of antimicrobial agents have demonstrated incompatibility with other agents commonly administered intravenously.

OBJECTIVE

To evaluate the physical compatibility and chemical stability of the novel lipopeptide antibiotic daptomycin, at 20 mg/mL, with 9 commonly administered intravenous medications: aztreonam, ceftazidime, ceftriaxone, dopamine, gentamicin, fluconazole, heparin, levofloxacin, and lidocaine to support simultaneous Y-site administration.

METHODS

Daptomycin was admixed with each medication separately in NaCl 0.9%, incubated at room temperature, and assayed at 30, 60, and 120 minutes. Physical stability was assessed by visual inspection and by turbidity measurements. Chemical stability was assessed by HPLC analysis using standard methods.

RESULTS

All 9 daptomycin admixtures remained clear solutions, free of visible particulates. There were also few changes in turbidity (range 0 to -0.7 nephelometric turbidity units) during the study. In general, pH changes were within +/- 0.06 of baseline readings for all admixtures. HPLC analysis indicated no significant reduction (<4%) in daptomycin potency after 120 minutes at room temperature compared with baseline values in all 9 admixtures tested. In addition, there was no significant reduction (<5%) in potency compared with baseline values of the 9 medications tested in the daptomycin admixtures.

CONCLUSIONS

The results of this study indicate that solutions of 9 commonly administered intravenous medications simultaneously Y-site administered with daptomycin are stable and compatible, based on both physical and chemical potency analyses.

摘要

背景

患有严重革兰氏阳性菌感染的住院患者往往需要联合治疗。不幸的是,一些抗菌药物已被证明与其他常用的静脉给药药物不相容。

目的

评估新型脂肽抗生素达托霉素(浓度为20mg/mL)与9种常用静脉药物:氨曲南、头孢他啶、头孢曲松、多巴胺、庆大霉素、氟康唑、肝素、左氧氟沙星和利多卡因的物理相容性和化学稳定性,以支持同时进行Y型接口给药。

方法

将达托霉素分别与每种药物在0.9%氯化钠溶液中混合,在室温下孵育,并在30、60和120分钟时进行检测。通过目视检查和浊度测量评估物理稳定性。使用标准方法通过高效液相色谱分析评估化学稳定性。

结果

所有9种达托霉素混合物仍为澄清溶液,无可见颗粒。在研究过程中,浊度变化也很小(范围为0至-0.7散射浊度单位)。一般来说,所有混合物的pH值变化在基线读数±0.06范围内。高效液相色谱分析表明,与所有9种测试混合物的基线值相比,达托霉素在室温下120分钟后的效价没有显著降低(<4%)。此外,与达托霉素混合物中测试的9种药物的基线值相比,效价也没有显著降低(<5%)。

结论

本研究结果表明,基于物理和化学效价分析,9种常用静脉药物与达托霉素同时进行Y型接口给药的溶液是稳定且相容的。

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