Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA.
Department of Medicine, National University Hospital, Singapore.
J Antimicrob Chemother. 2014 Sep;69(9):2517-21. doi: 10.1093/jac/dku143. Epub 2014 May 5.
Ertapenem is a broad-spectrum carbapenem antibiotic used to treat severe bacterial infections. In view of its dosing convenience, it is increasingly used as outpatient therapy. The objective of this study was to determine the pharmacokinetics and renal disposition of ertapenem in outpatients with complicated urinary tract infections.
Ertapenem was administered as a daily intravenous infusion of 1 g over 30 min. At steady-state, blood and urine samples were collected over one dosing interval. Drug concentrations in serum and urine were determined using a validated liquid chromatography-tandem mass spectrometry method. A population pharmacokinetic model was used to characterize ertapenem serum and urine profiles. The likelihood of the standard dosing achieving a favourable pharmacokinetic-pharmacodynamic exposure was evaluated using Monte Carlo simulations.
Ten adult male patients were studied. Concentration-time profiles of ertapenem in both serum (r(2) =0.997) and urine (r(2) =0.982) were captured satisfactorily. Mean values for volume of distribution, clearance and elimination t½ were 4.8 L, 0.7 L/h and 6.1 h, respectively. A high ertapenem concentration (>128 mg/L) could be attained in the urine at 40% of the dosing interval.
The pharmacokinetics of ertapenem in serum and urine were characterized. Our simulations suggested that a sufficiently high ertapenem concentration could be achieved in urine to overcome low to intermediate resistance. Clinical investigations to validate our findings are warranted.
厄他培南是一种广谱碳青霉烯类抗生素，用于治疗严重细菌感染。鉴于其使用方便，它越来越多地被用作门诊治疗。本研究的目的是确定门诊复杂性尿路感染患者中厄他培南的药代动力学和肾排泄情况。
厄他培南每天静脉输注 1 克，持续 30 分钟。在稳态时，采集一个给药间隔内的血样和尿样。使用经过验证的液相色谱-串联质谱法测定血清和尿液中的药物浓度。使用群体药代动力学模型来描述厄他培南的血清和尿液特征。使用蒙特卡罗模拟评估标准剂量达到有利的药代动力学-药效学暴露的可能性。
研究了 10 名成年男性患者。厄他培南在血清（r(2) = 0.997）和尿液（r(2) = 0.982）中的浓度-时间曲线得到了很好的描述。分布容积、清除率和消除半衰期的平均值分别为 4.8 L、0.7 L/h 和 6.1 h。在 40%的给药间隔内，尿液中可达到较高的厄他培南浓度（>128 mg/L）。
描述了厄他培南在血清和尿液中的药代动力学。我们的模拟表明，尿液中可以达到足够高的厄他培南浓度，以克服低至中度耐药性。需要进行临床研究来验证我们的发现。
