Ohchi Yoshifumi, Hidaka Seigo, Goto Koji, Shitomi Ryo, Nishida Taichi, Abe Takakuni, Yamamoto Shunsuke, Yasuda Norihisa, Hagiwara Satoshi, Noguchi Takayuki
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Oita University, Oita, Japan.
Yakugaku Zasshi. 2011;131(9):1395-9. doi: 10.1248/yakushi.131.1395.
Hemopurification is an effective therapy for acute kidney injury, defined as creatinine clearance less than 30 ml/min, which occurs frequently in the intensive care unit. These critically ill patients often have severe infectious complications and are thus often treated with antibiotics. However, the effect of hemopurification on the pharmacokinetics of antibiotics is not well understood. In this study, we investigated the pharmacokinetics of doripenem (DRPM) in critically ill patients with accompanying renal dysfunction undergoing continuous hemodiafiltration by high-volume filtration/high-flow dialysis (high-flow CHDF) and compared it to the pharmacokinetics of DRPM during conventional CHDF. We studied 8 patients (2 in the high-flow group and 6 in the conventional group) in whom DRPM was administered while performing CHDF for acute kidney injury. DRPM (250 mg) was intravenously infused over 1 h. For the conventional group, CHDF was performed at a blood flow rate (Q(B)) of 100 ml/min, dialysate flow rate (Q(D)) of 500 ml/h, and filtration flow rate (Q(F)) of 300 ml/h. For the high-flow group, CHDF was performed at a blood flow rate (Q(B)) of 100 ml/min, dialysate flow rate (Q(D)) of 1500 ml/h, and filtration flow rate (Q(F)) of 900 ml/h. For both groups, a polysulfonehemofilter with a membrane area of 1.0 m(2) was used. Mean half-life, total body clearance, and clearance via hemodiafiltration of DRPM were 2.9 h, 118 ml/min, and 41.9 ml/min, respectively, in the high-flow group, and 7.9 h, 58 ml/min, and 13.5 ml/min in the conventional group. Clearance via hemodiafiltration increased approximately 3-fold by tripling the hemopurification rate. Therefore, CHDF parameters greatly affected DRPM pharmacokinetics in patients receiving CHDF. These results suggest that clearance via hemodiafiltration increases proportionally to the hemopurification rate. Thus, it is reasonable to conclude that DRPM dose must be increased to 1.0-1.5 g/day when performing high-flow CHDF.
血液净化是治疗急性肾损伤的有效方法，急性肾损伤定义为肌酐清除率低于30 ml/分钟，这在重症监护病房中经常发生。这些重症患者往往有严重的感染并发症，因此常接受抗生素治疗。然而，血液净化对抗生素药代动力学的影响尚不清楚。在本研究中，我们调查了在接受高容量滤过/高流量透析（高流量连续性血液透析滤过，high-flow CHDF）的伴有肾功能不全的重症患者中多利培南（doripenem，DRPM）的药代动力学，并将其与传统CHDF期间DRPM的药代动力学进行比较。我们研究了8例在进行急性肾损伤的CHDF时给予DRPM的患者（高流量组2例，传统组6例）。DRPM（250 mg）在1小时内静脉输注。对于传统组，CHDF以100 ml/分钟的血流量（Q(B)）、500 ml/小时的透析液流速（Q(D)）和300 ml/小时的滤过流速（Q(F)）进行。对于高流量组，CHDF以100 ml/分钟的血流量（Q(B)）、1500 ml/小时的透析液流速（Q(D)）和900 ml/小时的滤过流速（Q(F)）进行。两组均使用膜面积为1.0 m(2)的聚砜血液滤过器。在高流量组中，DRPM的平均半衰期、全身清除率和血液透析滤过清除率分别为2.9小时、118 ml/分钟和41.9 ml/分钟，在传统组中分别为7.9小时、58 ml/分钟和13.5 ml/分钟。通过将血液净化率提高两倍，血液透析滤过清除率增加了约3倍。因此，CHDF参数对接受CHDF的患者的DRPM药代动力学有很大影响。这些结果表明，血液透析滤过清除率与血液净化率成比例增加。因此，合理的结论是，在进行高流量CHDF时，DRPM剂量必须增加到1.0 - 1.5 g/天。
