Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
Ann Pharmacother. 2010 Mar;44(3):557-64. doi: 10.1345/aph.1M339. Epub 2010 Feb 2.
To systematically review evidence comparing traditional and alternative dosing strategies for meropenem, based on clinical and pharmacoeconomic outcomes.
MEDLINE (1950-September 2009), EMBASE (1980-September 2009), and International Pharmaceutical Abstracts (1970-September 2009) were searched, using the terms meropenem, carbapenems, pharmacodynamics, and pharmacokinetics. Reference citations from publications identified were reviewed.
Articles discussing administration of meropenem to adults with normal renal function and comparing at least 2 regimens, 1 of which included the manufacturer-recommended regimen of 0.5 g or 1 g every 8 hours infused over 30 minutes, with clinical, pharmacodynamic, or pharmacoeconomic endpoints, were included. The pharmacodynamic endpoint of interest was percent time that the unbound drug concentration exceeded the minimal inhibitory concentration for a bacterial pathogen.
Sixteen studies were reviewed, which included 13 pharmacokinetic and dynamic assessments using Monte Carlo simulations, 5 clinical evaluations, and 3 pharmacoeconomic appraisals. Data on clinical and economic outcomes are largely nonrandomized retrospective analyses and case reports. Meropenem via intermittent prolonged infusion potentially increases the likelihood of achieving pharmacodynamic targets. However, a strong link with improved clinical outcomes is lacking. Smaller doses with shorter intervals appear to provide pharmacodynamic target attainment rates and clinical outcomes similar to those with traditional dosing, with potential pharmacoeconomic benefits. Meropenem via continuous infusion appears to increase the likelihood of achieving pharmacodynamic targets, compared with intermittent infusions. The sparsity of clinical evidence supporting this practice limits its broad application to practice. No studies have formally examined adverse effects with alternative dosing regimens.
Meropenem alternative dosing strategies provide similar pharmacodynamic target attainment rates compared with traditional dosing strategies. Small doses with shorter interval dosing provide additional pharmacoeconomic benefits and similar clinical outcomes. Alternative dosing strategies for meropenem were largely studied in healthy subjects; individuals with pharmacokinetic parameters that differ significantly may be ideal subjects for empiric dose modification.
系统评价比较美罗培南传统与替代给药方案的临床和药物经济学结局的证据。
检索 MEDLINE（1950 年-2009 年 9 月）、EMBASE（1980 年-2009 年 9 月）和国际药学文摘（1970 年-2009 年 9 月），使用美罗培南、碳青霉烯类、药效学和药代动力学等术语。查阅已发表文献的参考文献。
纳入讨论美罗培南在肾功能正常的成年人中的应用，且比较至少 2 种方案，其中 1 种方案包含制造商推荐的方案，即 0.5 g 或 1 g 每 8 小时输注 30 分钟，有临床、药效学或药物经济学终点的文章。关注的药效学终点是未结合药物浓度超过细菌病原体最小抑菌浓度的时间百分比。
综述了 16 项研究，包括 13 项使用蒙特卡罗模拟的药代动力学和药效学评估、5 项临床评价和 3 项药物经济学评价。临床和经济结局的数据主要是非随机回顾性分析和病例报告。美罗培南通过间歇性延长输注可能增加达到药效学目标的可能性。然而，与改善临床结局之间缺乏强有力的联系。较小剂量、较短间隔给药方案似乎能达到与传统给药方案相似的药效学目标和临床结局，同时具有潜在的药物经济学效益。与间歇性输注相比，连续输注似乎能增加达到药效学目标的可能性。支持这种实践的临床证据很少，限制了其在实践中的广泛应用。没有研究正式检查替代给药方案的不良反应。
美罗培南替代给药方案与传统给药方案相比，提供相似的药效学目标达标率。小剂量、较短间隔给药方案提供了额外的药物经济学效益和相似的临床结局。美罗培南的替代给药方案主要在健康受试者中进行研究；药代动力学参数显著不同的个体可能是经验性剂量调整的理想对象。
