Gous A G, Dance M D, Lipman J, Luyt D K, Mathivha R, Scribante J
Department of Pharmacy, University of the Witwatersrand, Johannesburg, South Africa.
Anaesth Intensive Care. 1995 Dec;23(6):678-82. doi: 10.1177/0310057X9502300603.
We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose of 10 mg/kg 6 hourly. All infants admitted to the Baragwanath Hospital ICU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescribed for an infective insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy. Extrapolated peak concentration (Cmax), trough concentration (Cmin), apparent volume of distribution (Vd), elimination half-life (t1/2el) and clearance (CL) were determined for each patient. Day 2 values were compared with those of day 8. Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15. The mean vancomycin Vd on day 2 (0.81 l/kg) was significantly (P = 0.007) larger than that on day 8 (0.44 l/kg). The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 micrograms/ml) (P = 0.02) and mean t1/2el (5.3 vs 3.4h) (P = 0.01) over the treatment period. Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation. This also results in a large variation in other pharmacokinetic parameters, namely Cmax and t1/2el. Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.
我们旨在评估万古霉素在重症婴儿中的药代动力学，并评估每6小时10mg/kg的标准推荐剂量。纳入了所有入住巴拉格瓦纳特医院重症监护病房、留置动脉导管、因感染性损伤而接受每6小时10mg/kg万古霉素治疗且获得家长同意的婴儿。万古霉素输注时间为60分钟。在治疗的第2天和第8天，在给药前以及万古霉素输注结束后30、60、120和300分钟采集血清样本。测定每位患者的外推峰浓度（Cmax）、谷浓度（Cmin）、表观分布容积（Vd）、消除半衰期（t1/2el）和清除率（CL）。比较第2天和第8天的值。对20例患者测定了第2天的血清浓度，15例患者测定了第8天的浓度。第2天万古霉素的平均Vd（0.81l/kg）显著高于第8天（0.44l/kg）（P = 0.007）。在治疗期间，Vd的变化导致平均Cmax（29.1对35.5μg/ml）（P = 0.02）和平均t1/2el（5.3对3.4小时）（P = 0.01）发生显著变化。重症婴儿表现出较大的初始分布容积，这可能是积极液体复苏的结果。这也导致其他药代动力学参数，即Cmax和t1/2el出现较大差异。尽管万古霉素血清浓度的常规监测仍存在争议，但鉴于这些较大的药代动力学差异，我们认为重症婴儿是一个需要监测万古霉素血清水平的特殊群体。
