Wallace Allison Wood, Jones Matthew, Bertino Joseph S
Department of Pharmacy Services, Bassett Healthcare, Cooperstown, New York 13326, USA.
Pharmacotherapy. 2002 Sep;22(9):1077-83. doi: 10.1592/phco.22.13.1077.33529.
To evaluate the accuracy of four once-daily aminoglycoside dosing nomograms in producing the desired gentamicin peak concentration (Cmax) target of 20 microg/ml in patients with varying degrees of renal function.
Retrospective analysis using prospectively collected pharmacokinetic data.
Rural teaching hospital.
Ninety patients receiving intravenous gentamicin divided into three groups (30 patients each) determined by estimated renal function: group 1, creatinine clearance (Cl(cr),) 60 ml/minute or greater; group 2, Cl(cr) 40-59 ml/minute; group 3, Cl(cr) 20-39 ml/minute. Intervention. Serum gentamicin concentrations were collected for a 2-point (two consecutive infusions and one predose and one postdose concentration sampled during steady state) or 3-point (single infusion and one predose and two postdose concentrations at least 1.5 estimated half-lives apart) pharmacokinetic study for determination of patient-specific pharmacokinetic parameters (elimination rate constant, volume of distribution at steady state, and clearance) after 30-minute infusions of gentamicin 2.8 +/- 1.6 mg/kg.
The four nomograms evaluated were from Hartford Hospital, Barnes-Jewish Hospital, University of Rochester, and the Sanford Guide. With a pharmacokinetic analysis program and the patient-specific pharmacokinetic parameters, Cmax and minimum concentration (Cmin) were determined with use of the recommended doses and dosing intervals of the four nomograms. Also, the gentamicin dose and interval needed to achieve a Cmax and Cmin of 20 microg/ml and 0.2 microg/ml, respectively, were determined. Dosing was based on total body weight unless that weight was more than 25% of ideal body weight, in which case, an adjusted body weight was used. In general, the recommended dosages and resultant Cmax produced by the nomograms were significantly less (p < 0.05) than the dosage and Cmax actually needed to achieve a Cmax:minimum inhibitory concentration (MIC) ratio of 10 or greater for bacteria with an MIC of 2 microg/ml.
Once-daily aminoglycoside dosing using the four nomograms resulted in inaccurate dosing, and because of the large variability in human pharmacokinetics, dosing nomograms such as these should be abandoned in favor of individualizing dosages with therapeutic drug monitoring.
评估四种每日一次氨基糖苷类药物给药剂量图在不同肾功能程度患者中产生目标庆大霉素峰浓度（Cmax）20μg/ml的准确性。
使用前瞻性收集的药代动力学数据进行回顾性分析。
农村教学医院。
90例接受静脉注射庆大霉素的患者，根据估计的肾功能分为三组（每组30例）：第1组，肌酐清除率（Cl(cr)）60ml/分钟或更高；第2组，Cl(cr) 40 - 59ml/分钟；第3组，Cl(cr) 20 - 39ml/分钟。干预措施。采集血清庆大霉素浓度用于两点（两次连续输注以及稳态期间一次给药前和一次给药后浓度）或三点（单次输注以及一次给药前和两次给药后浓度，至少相隔1.5个估计半衰期）药代动力学研究，以确定在输注2.8±1.6mg/kg庆大霉素30分钟后患者特异性药代动力学参数（消除速率常数、稳态分布容积和清除率）。
评估的四种剂量图分别来自哈特福德医院、巴恩斯 - 犹太医院、罗切斯特大学和《桑福德指南》。使用药代动力学分析程序和患者特异性药代动力学参数，根据四种剂量图的推荐剂量和给药间隔确定Cmax和最低浓度（Cmin）。此外，还确定了分别达到Cmax 20μg/ml和Cmin 0.2μg/ml所需的庆大霉素剂量和间隔。给药基于总体重，除非该体重超过理想体重的25%，在这种情况下，使用调整体重。一般而言，剂量图产生的推荐剂量和由此产生的Cmax显著低于（p < 0.05）达到Cmax:最低抑菌浓度（MIC）比值为10或更高（针对MIC为2μg/ml的细菌）实际所需的剂量和Cmax。
使用这四种剂量图进行每日一次氨基糖苷类药物给药导致给药不准确，并且由于人体药代动力学存在很大变异性，此类给药剂量图应被摒弃，转而采用治疗药物监测来个体化给药剂量。
