Fawaz Sarah, Barton Stephen, Whitney Laura, Swinden Julian, Nabhani-Gebara Shereen
Kingston University, Kingston upon Thames, UK.
St George's University Hospitals NHS Foundation Trust, London, UK.
Hosp Pharm. 2019 Jun;54(3):190-196. doi: 10.1177/0018578718779009. Epub 2018 May 30.
Meropenem is a parenteral carbapenem antibiotic which has a broad spectrum of activity against aerobes and anaerobes. Meropenem's bactericidal activity is determined by the time during which meropenem concentration remains above the minimal inhibition concentration (MIC) during the dosing interval. Thus, prolonged infusion is the optimal way to maximize the time-dependant activity. However, studies to date have shown that carbapenems and in particular, meropenem, are relatively unstable in solution. The aims of this study were therefore (1) to establish the effects of temperature on the concentration of a generic brand reconstituted meropenem solution and (2) to determine whether 24-hour continuous infusion is possible without concentrations dropping below the recommended 90%. Preliminary examination was carried out by the means of nuclear magnetic resonance (NMR) spectroscopy. Meropenem was subsequently assayed using high-performance liquid chromatography (HPLC). The method was developed and validated in compliance with International Council for Harmonisation (ICH) guidelines. Meropenem's stability was examined at two temperatures 22°C and 33°C to mimic average and high temperature in hospital wards. Solutions were prepared aseptically at the clinically relevant concentration. NMR results obtained showed an increase in open ring methyl groups peak intensity, indicating that meropenem begins to degrade upon dissolution (d=1.05 and 1.25). Results obtained from quantitative HPLC confirm that meropenem concentrations dropped to 90% of initial concentration at 7.4 hours and 5.7 hours at 22°C and 33°C, respectively. Although results obtained indicate that meropenem should not be continuously infused over 24 hours, it is possible that meropenem could be continuously infused for at least 7 hours if temperature does not exceed 22°C and for 5 hours if temperature does not exceed 33°C.
美罗培南是一种肠胃外给药的碳青霉烯类抗生素，对需氧菌和厌氧菌均有广谱抗菌活性。美罗培南的杀菌活性取决于给药间隔期间美罗培南浓度保持高于最低抑菌浓度（MIC）的时间。因此，延长输注时间是使时间依赖性活性最大化的最佳方法。然而，迄今为止的研究表明，碳青霉烯类药物，尤其是美罗培南，在溶液中相对不稳定。因此，本研究的目的是：（1）确定温度对某普通品牌复溶美罗培南溶液浓度的影响；（2）确定是否可以进行24小时持续输注而不使浓度降至推荐的90%以下。初步检查通过核磁共振（NMR）光谱法进行。随后使用高效液相色谱法（HPLC）对美罗培南进行测定。该方法按照国际协调理事会（ICH）指南进行开发和验证。在22°C和33°C这两个温度下检测美罗培南的稳定性，以模拟医院病房的平均温度和高温。以临床相关浓度无菌制备溶液。获得的NMR结果显示开环甲基峰强度增加，表明美罗培南在溶解时开始降解（d = 1.05和1.25）。定量HPLC获得的结果证实，在22°C和33°C下，美罗培南浓度分别在7.4小时和5.7小时降至初始浓度的90%。虽然获得的结果表明美罗培南不应连续输注超过24小时，但如果温度不超过22°C，美罗培南有可能连续输注至少7小时；如果温度不超过33°C，则可能连续输注5小时。
