Khaleel Israa, Zaidi Syed Tabish R, Shastri Madhur D, Eapen Mathew Suji, Ming Long Chiau, Wanandy Troy, Patel Rahul P
School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Pharmacy, Royal Hobart Hospital, Hobart, Tasmania, Australia.
Eur J Hosp Pharm. 2018 Oct;25(e2):e102-e108. doi: 10.1136/ejhpharm-2017-001225. Epub 2017 Jul 19.
High dose of intravenous sulfamethoxazole and trimethoprim (co-trimoxazole) is often used in immunocompromised patients for the treatment of pneumonia. Current manufacturer's dilution recommendation for intravenous co-trimoxazole (1:25 v/v) requires the administration of 2 L of additional fluid per day causing serious complications including pulmonary oedema. Intravenous administration of concentrated solution of co-trimoxazole may minimise the risk of fluid overload associated side effects. Therefore, the objective of the study was to investigate the physicochemical stability of concentrated intravenous co-trimoxazole solutions.
Four ampoules of intravenous co-trimoxazole were injected into an infusion bag containing either 480 (1:25 v/v), 380 (1:20 v/v), 280 (1:15 v/v) or 180 (1:10 v/v) mL of glucose 5% solution. Three bags for each dilution (total 12 bags) were prepared and stored at room temperature. An aliquot was withdrawn immediately (at 0 hour) and after 0.5, 1, 2 and 4 hours of storage for high-performance liquid-chromatography (HPLC) analysis, and additional samples were withdrawn every half an hour for microscopic examination. Each sample was analysed for the concentration of trimethoprim and sulfamethoxazole using a stability indicating HPLC method. Samples were assessed for pH, change in colour (visually) and for particle content (microscopically) immediately after preparation and on each time of analysis.
Intravenous co-trimoxazole at 1:25, 1:20, 1:15 and 1:10 v/v retained more than 98% of the initial concentration of trimethoprim and sulfamethoxazole for 4 hours. There was no major change in pH at time zero and at various time points. Microscopically, no particles were detected for at least 4 hours and 2 hours when intravenous co-trimoxazole was diluted at 1:25 or 1:20 and 1:15 v/v, respectively. More than 1200 particles/mL were detected after 2.5 hours of storage when intravenous co-trimoxazole was diluted at 1:15 v/v.
Intravenous co-trimoxazole is stable over a period of 4 hours when diluted with 380 mL of glucose 5% solution (1:20 v/v) and for 2 hours when diluted with 280 mL glucose 5% solution (1:15 v/v).
高剂量静脉注射磺胺甲恶唑和甲氧苄啶（复方新诺明）常用于免疫功能低下患者的肺炎治疗。目前制造商推荐的静脉注射复方新诺明的稀释比例（1:25 v/v）要求每天额外输注2L液体，这会引发包括肺水肿在内的严重并发症。静脉注射浓缩复方新诺明溶液可能会降低液体超负荷相关副作用的风险。因此，本研究的目的是调查浓缩静脉注射复方新诺明溶液的物理化学稳定性。
将四支静脉注射用复方新诺明安瓿注入分别装有480（1:25 v/v）、380（1:20 v/v）、280（1:15 v/v）或180（1:10 v/v）mL 5%葡萄糖溶液的输液袋中。每种稀释度制备三袋（共12袋）并在室温下储存。立即（0小时）以及储存0.5、1、2和4小时后取出等分试样用于高效液相色谱（HPLC）分析，每隔半小时取出额外样品用于显微镜检查。使用稳定性指示HPLC法分析每个样品中甲氧苄啶和磺胺甲恶唑的浓度。在制备后及每次分析时，对样品进行pH值、颜色变化（目视）和颗粒含量（显微镜检查）评估。
1:25、1:20、1:15和1:10 v/v的静脉注射复方新诺明在4小时内保留了超过98%的初始甲氧苄啶和磺胺甲恶唑浓度。在时间零点和各个时间点，pH值没有重大变化。显微镜检查显示，当静脉注射复方新诺明分别以1:25或1:20和1:15 v/v稀释时，至少4小时和2小时内未检测到颗粒。当静脉注射复方新诺明以1:15 v/v稀释时，储存2.5小时后检测到每毫升超过1200个颗粒。
静脉注射复方新诺明用380 mL 5%葡萄糖溶液（1:20 v/v）稀释时在4小时内稳定，用280 mL 5%葡萄糖溶液（1:15 v/v）稀释时在2小时内稳定。
