Pharmacokinetics of cefepime during continuous renal replacement therapy in critically ill patients
Pharmacokinetics of cefepime during continuous renal replacement therapy in critically ill patients
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DOI：
10.1128/aac.45.11.3148-3155.2001
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发表时间：
2001-11-01
影响因子：
4.9
通讯作者：
Teitelbaum, I
中科院分区：
文献类型：
--
作者：
Malone, RS;Fish, DN;Teitelbaum, I
应用Multiflow 60 AN69HF 0.60-m(2)聚丙烯腈中空纤维膜(法国Meyzieu医院)，对12例重症监护病房成人患者在连续性静脉-静脉血液滤过(CVN-H)和连续性静脉-静脉血液透析滤过(CVVHDF)中的药代动力学进行了研究。患者(平均年龄52.0±13.0岁[标准差]；平均体重96.7±18.4 kg)，每12或24 h静脉滴注头孢吡肟1~2g，每日1~4g，持续静脉滴注15~30min。分别于给药结束后1、2、4、8、12或24 h采集膜前、膜后血(血清)及相应的超滤液或透析液样品。药物浓度用经过验证的高效液相色谱方法测量。CVVH组和CVVHDF组的平均系统清除率(CLS)和消除半衰期(t(1/2))分别为35.9±6.0ml/min和12.9±2.6h，CVVHDF组分别为46.8±12.4ml/min和8.6±1.4h。在CVVH和CVVHDF中，头孢吡肟的清除量均显著增加，膜清除量分别为CLS的40%和59%。这项研究的结果证实，连续性肾脏替代疗法对头孢吡肟的总CLS有很大贡献，而且CVVHDF似乎比CVVH更有效地去除头孢吡肟。在CVVH或CVVHDF期间，2克/天的头孢吡肟剂量(每天2克/天或1克/天两次)似乎达到足以治疗大多数常见革兰氏阴性病原体(MIC小于或等于8微克/毫升)的浓度。
The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVN H) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m(2) polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 +/- 13.0 years [standard deviation]; mean weight, 96.7 +/- 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CLs) and elimination half-life (t(1/2)) of cefepime were 35.9 +/- 6.0 ml/min and 12.9 +/- 2.6 h during CVVH versus 46.8 +/- 12.4 ml/min and 8.6 +/- 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CLS, respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CLs of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC less than or equal to 8 mug/ml) during CVVH or CVVHDF.