Hashimoto S, Honda M, Yamaguchi M, Sekimoto M, Tanaka Y
Department of Anesthesiology and Intensive Carer Medicine, Kyoto Prefectural University of Medicine, Japan.
ASAIO J. 1997 Jan-Feb;43(1):84-8.
The objective of this study is to study the pharmacokinetics of imipenem-cilastatin in patients with anuria related to multiorgan failure during continuous venovenous hemodialysis (CVVHD) at a fixed blood flow rate of 60 ml/min, fixed dialysate flow rate of 20 ml/min, and drainage flow rate of 1-3 mil/min. A prospective open label study was designed in an intensive care unit in a university hospital. Six patients who required mechanical ventilation and inotropic agents and exhibited acute anuric renal failure were examined. Intravenous imipenem-cilastatin, 500/500 mg, was administered over 30 mins. Blood samples were obtained from the inlet and the outlet of the dialyzer and dialysate samples from the outlet before and at 0.0, 0.5, 1.0, 2.0, 3.0, 6.0, 9.0, and 12.0 hrs after infusion ended. The peak and trough concentrations of imipenem were 32.47 +/- 6.69 micrograms/ml and 1.12 +/- 0.46 micrograms/ml, respectively, whereas those of cilastatin were 50.05 micrograms/ml +/- 14.80 and 9.53 +/- 3.25 micrograms/ml, respectively. The half life was 2.79 +/- 0.3 hr for imipenem, and 6.67 +/- 0.93 hr for cilastatin. Total body clearance of imipenem was 89.4 +/- 17.5 ml/min, including the clearance by CVVHD of 18.7 +/- 1.2 ml/min, and corresponding values for cilastatin were 31.7 +/- 9.0 ml/min and 13.7 +/- 3.4 ml/min. In conclusion, in patients with anuria, the elimination of imipenem-cilastatin was constant during CVVHD. The recommended regimen in patients with anuria who receive CVVHD in this setting was estimated as intravenous imipenem-cilastatin, 500/500 mg, every 12 hrs.
本研究的目的是在持续静静脉血液透析（CVVHD）过程中，以60毫升/分钟的固定血流速度、20毫升/分钟的固定透析液流速和1 - 3毫升/分钟的引流流速，研究亚胺培南 - 西司他丁在多器官功能衰竭所致无尿患者中的药代动力学。在一所大学医院的重症监护病房设计了一项前瞻性开放标签研究。对6例需要机械通气和使用血管活性药物且表现为急性无尿性肾衰竭的患者进行了检查。静脉输注500/500毫克亚胺培南 - 西司他丁，输注时间为30分钟。在透析器入口和出口采集血样，并在输注结束前以及结束后0.0、0.5、1.0、2.0、3.0、6.0、9.0和12.0小时从透析液出口采集透析液样本。亚胺培南的峰浓度和谷浓度分别为32.47±6.69微克/毫升和1.12±0.46微克/毫升，而西司他丁的峰浓度和谷浓度分别为50.05微克/毫升±14.80和9.53±3.25微克/毫升。亚胺培南的半衰期为2.79±0.3小时，西司他丁的半衰期为6.67±0.93小时。亚胺培南的总体清除率为89.4±17.5毫升/分钟，其中通过CVVHD的清除率为18.7±1.2毫升/分钟，西司他丁的相应值分别为31.7±9.0毫升/分钟和13.7±3.4毫升/分钟。总之，在无尿患者中，CVVHD期间亚胺培南 - 西司他丁的清除是恒定的。在此情况下，接受CVVHD的无尿患者的推荐给药方案估计为每12小时静脉输注500/500毫克亚胺培南 - 西司他丁。
