Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration
Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration
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DOI：
10.1111/j.1365-2125.2004.02143.x
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发表时间：
2004-09-01
影响因子：
3.4
通讯作者：
Tett, SE
中科院分区：
文献类型：
--
作者：
DelDot, ME;Lipman, J;Tett, SE
目的研究万古霉素在接受连续性静脉-静脉血液透析滤过（CVVHDF）的危重患者中的药代动力学，连续性肾脏替代治疗（CRRT），并观察常规措施是否接近万古霉素清除率。从10名重症患者的血液和超滤液样本中获得了750 mg每日两次静脉注射万古霉素的状态剂量，结果CVVHDF对万古霉素的清除率为1.8+/-0.4 l h（-1）（30+/-6.7 ml min（-1））。这是之前使用其他形式CRRT报告的万古霉素的1.3-7.2倍。万古霉素的总体清除率为2.5+/-0.7 l h（-1）（41.7+/-11.7 ml min（-1））。CVVHDF对万古霉素的清除率为全身清除率的76+/-16.5%。CVVHDF在12小时内清除了约一半的万古霉素剂量（A（CVVHDF）=413 mg）。所有途径消除的分数为60%。万古霉素的筛分系数为0.7 ± 0.1，尿素的筛分系数为0.8 ± 0.06。结论CVVHDF可有效清除万古霉素。清除速度快于其他形式的CRRT，因此需要相对较高的剂量。尿素清除率略微高估万古霉素清除率。750 mg每12 h给药一次的剂量过高，并发生蓄积，因为在此期间仅约60%的剂量被清除。达到目标平均稳态血药浓度15 mg l（-1）所需的维持剂量可计算为每12 h 450 mg。
Aims To investigate the pharmacokinetics of vancomycin in critically ill patients on continuous venovenous haemodiafiltration (CVVHDF), a continuous renal replacement therapy (CRRT) and to see if routine measures approximate vancomycin clearance.Methods Pharmacokinetic profiles (15) of initial and steady-state doses of 750 mg twice daily intravenous vancomycin were obtained from blood and ultrafiltrate samples from 10 critically ill patients in the intensive care unit, with acute renal failure on CVVHDF (1 l h(-1) dialysate plus 2 l h(-1) filtration solution; 3 l h(-1) effluent; extracorporeal blood flow 200 ml min(-1)).Results CVVHDF clearance of vancomycin was 1.8+/-0.4 l h(-1) (30+/-6.7 ml min(-1)). This was 1.3-7.2 times that reported previously for vancomycin using other forms of CRRT. Total vancomycin body clearance was 2.5+/-0.7 l h(-1) (41.7+/-11.7 ml min(-1)). The clearance of vancomycin by CVVHDF was 76+/-16.5% of the total body clearance. CVVHDF removed approximately half the vancomycin dose during the 12-h period (A(CVVHDF)=413 mg). The fraction eliminated by all routes was 60%. The sieving coefficient for vancomycin was 0.7+/-0.1 and for urea was 0.8+/-0.06.Conclusions Vancomycin is cleared effectively by CVVHDF. Clearance was faster than other forms of CRRT, therefore doses need to be relatively high. Urea clearance slightly overestimates vancomycin clearance. The administered doses of 750 mg every 12 h were too high and accumulation occurred, as only approximately 60% of a dose was cleared over this period. The maintenance dose required to achieve a target average steady-state plasma concentration of 15 mg l(-1) can be calculated as 450 mg every 12 h.