Beckhouse M J, Whyte I M, Byth P L, Napier J C, Smith A J
Discipline of Clinical Pharmacology, Faculty of Medicine, University of Newcastle.
Anaesth Intensive Care. 1988 Nov;16(4):418-22. doi: 10.1177/0310057X8801600406.
We studied prospectively 49 patients being treated in an intensive care unit with aminoglycosides for gram-negative sepsis. Pharmacokinetic data were calculated from three post-dose serum levels using a one-compartment model. Doses required to achieve peak levels between 5 and 10 mg/l with trough levels approximately 1.0 mg/l ranged between 2 and 12 mg/kg per day (mean dose 7 mg/kg per day). During therapy 60% of the patients had a change in their apparent volume of distribution (Vd) of greater than 20%. These patients were likely to have confirmed infection and to be febrile at the start of treatment. Two to three weeks after discharge ten patients were restudied after a single dose of aminoglycoside. There was a reduction in mean Vd from 0.24 to 0.18 l/kg (P less than 0.02). Critically ill patients have significantly larger volumes of distribution and may require larger doses per kilogram of body weight of aminoglycoside to achieve therapeutic concentrations. Due to considerable variation in kinetic parameters, the use of standard doses or dosing nomograms is not recommended.
我们前瞻性地研究了49例在重症监护病房接受氨基糖苷类药物治疗革兰氏阴性菌败血症的患者。使用单室模型根据给药后三个血清水平计算药代动力学数据。达到5至10mg/L的峰值水平且谷值水平约为1.0mg/L所需的剂量范围为每天2至12mg/kg（平均剂量7mg/kg/天）。在治疗期间，60%的患者其表观分布容积（Vd）变化大于20%。这些患者在治疗开始时可能已确诊感染且发热。出院两到三周后，对10例患者给予单剂量氨基糖苷类药物后再次进行研究。平均Vd从0.24降至0.18L/kg（P<0.02）。重症患者的分布容积明显更大，可能需要每公斤体重更大剂量的氨基糖苷类药物才能达到治疗浓度。由于动力学参数存在相当大的差异，不建议使用标准剂量或给药方案。
