Carr Roxane R, Decarie Diane, Ensom Mary H H
, BSc(Pharm), ACPR, PharmD, FCSHP, BCPS, is Clinical Coordinator in the Department of Pharmacy, Children's and Women's Health Centre of British Columbia, and Assistant Professor, part-time, with the Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia.
, BSc, is a Research Consultant with the Department of Pharmacy, Children's and Women's Health Centre of British Columbia, Vancouver, British Columbia.
Can J Hosp Pharm. 2014 May;67(3):197-202. doi: 10.4212/cjhp.v67i3.1356.
To minimize medication errors, standard concentrations are recommended for medications intended for continuous infusion in pediatric patients. Premixing of epinephrine (commonly used to manage septic shock in children) would improve timeliness, safety, and cost-effectiveness. However, information about the stability of epinephrine at standard concentrations is limited.
To evaluate the stability of epinephrine in 5% dextrose in water at standard concentrations and to extend its expiration date after storage in infusion bags at 4°C and 25°C for up to 30 days.
A total of 6 infusion bags were prepared with 200 mL of epinephrine solution, 2 bags for each of 3 standard concentrations (25, 50, and 100 μg/mL). Three bags (one for each concentration) were stored under refrigeration (4°C), and the remaining 3 bags were stored at room temperature (25°C). Physical characteristics (including pH, colour, and presence of precipitate) were evaluated daily for the first 14 days and every 1 to 5 days thereafter until day 30. Three 1.5-mL samples were collected from each bag immediately after preparation (time 0), every 24 h (at 24 h, 48 h, 72 h, 96 h, etc.) for the first 14 days, and every 1 to 5 days thereafter until day 30. Each sample was analyzed by stability-indicating high-performance liquid chromatography. A solution was considered stable if it maintained at least 90% of its initial concentration.
No notable changes in pH, colour, or precipitation were observed in any of the solutions after storage at 4°C or 25°C for up to 30 days. All formulations maintained more than 95% of the initial epinephrine concentration on day 30. In addition, the calculated lower limit of the 95% confidence interval indicated that 93% or more of the initial concentration remained on day 30.
Preparations of epinephrine were stable for up to 30 days, with or without refrigeration. Because stability alone does not guarantee bioavailability or efficacy of a drug, future clinical studies are recommended to evaluate the pharmacokinetics and pharmacodynamics of these formulations.
为尽量减少用药错误，建议为儿科患者连续输注的药物设定标准浓度。肾上腺素预混液（常用于治疗儿童感染性休克）可提高及时性、安全性和成本效益。然而，关于标准浓度下肾上腺素稳定性的信息有限。
评估标准浓度的肾上腺素在5%葡萄糖水溶液中的稳定性，并延长其在4°C和25°C的输液袋中储存长达30天的有效期。
共制备6个装有200 mL肾上腺素溶液的输液袋，3种标准浓度（25、50和100 μg/mL）各2袋。3袋（每种浓度1袋）冷藏（4°C）保存，其余3袋室温（25°C）保存。在第14天前每天评估物理特性（包括pH值、颜色和沉淀情况），之后每1至5天评估一次，直至第30天。制备后立即（0小时）从每个袋子中采集3个1.5 mL样本，在第14天前每24小时（24小时、48小时、72小时、96小时等）采集一次，之后每1至5天采集一次，直至第30天。每个样本通过稳定性指示高效液相色谱法进行分析。如果溶液保持至少90%的初始浓度，则认为该溶液稳定。
在4°C或25°C下储存长达30天后，任何溶液的pH值、颜色或沉淀均未观察到明显变化。所有制剂在第30天保持了超过95%的初始肾上腺素浓度。此外，计算得出的95%置信区间下限表明，在第30天仍有93%或更多的初始浓度。
肾上腺素制剂在有或没有冷藏的情况下均可稳定保存30天。由于稳定性本身并不能保证药物的生物利用度或疗效，建议未来进行临床研究以评估这些制剂的药代动力学和药效学。
