Hidaka Seigo, Goto Koji, Hagiwara Satoshi, Iwasaka Hideo, Noguchi Takayuki
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Oita University, Yufu, Oita, Japan.
Yakugaku Zasshi. 2010 Jan;130(1):87-94. doi: 10.1248/yakushi.130.87.
Objectives of the prospective, open-label study were to investigate pharmacokinetics of doripenem and determine appropriate doripenem regimens during continuous hemodiafiltration (CHDF) in critically ill patients with renal failure (creatinine clearance <30 ml/min) in the intensive care unit at a university hospital in Japan. Six patients received intravenous (IV) administration of 250 mg of doripenem every 12 or 24 hours during CHDF (dialysis rate, 500 ml/h; hemofiltration rate, 300 ml/h) via a polysulfone hemofilter. Doripenem concentrations in pre- and post-membrane blood (plasma) samples collected at specified times during one dosing interval were measured in order to calculate pharmacokinetic parameters and clearance via hemodiafiltration. Mean half-life (+/-standard deviation) of doripenem was 7.9+/-3.7 hours. Total body clearance of doripenem was 58.0+/-12.7 ml/min, including clearance of 13.5+/-1.6 ml/min via CHDF. An IV dose of 250 mg of doripenem every 12 hours during CHDF provided adequate plasma concentrations for critically ill patients with renal failure, without resulting in accumulation upon steady-state. Thus, under the conditions tested, CHDF appeared to have little effect on doripenem clearance. Therefore, the blood level of doripenem can be satisfactorily controlled by adjustment of doripenem dose and dosing interval, in accordance with residual renal function in patients receiving CHDF.
这项前瞻性、开放标签研究的目的是，在日本一家大学医院的重症监护病房中，调查多利培南在肾衰竭（肌酐清除率<30 ml/min）的重症患者持续血液透析滤过（CHDF）期间的药代动力学，并确定合适的多利培南给药方案。6例患者在CHDF期间（透析率500 ml/h；血液滤过率300 ml/h）通过聚砜血液滤过器，每12或24小时静脉注射（IV）250 mg多利培南。在一个给药间隔内的特定时间采集膜前和膜后血液（血浆）样本中的多利培南浓度，以计算药代动力学参数和通过血液透析滤过的清除率。多利培南的平均半衰期（±标准差）为7.9±3.7小时。多利培南的总体清除率为58.0±12.7 ml/min，包括通过CHDF的清除率为13.5±1.6 ml/min。在CHDF期间每12小时静脉注射250 mg多利培南，可为肾衰竭的重症患者提供足够的血浆浓度，且在稳态时不会导致蓄积。因此，在所测试的条件下，CHDF似乎对多利培南清除率影响很小。所以，根据接受CHDF患者的残余肾功能，通过调整多利培南剂量和给药间隔，可以令人满意地控制多利培南的血药水平。
