Tsubaki T, Chandler M H
Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington.
Pharmacotherapy. 1994 May-Jun;14(3):330-6.
Aminoglycosides are widely used, and clinicians continue to seek newer and better methods for initial dosing of these agents. Recently, three new methods were introduced: Thomson, Reesor Nimmo, and dosing in renopathy by easy-to-use multipliers (DREM). In comparing them with older, traditional dosing methods in patients with various degrees of renal function, the pharmacokinetic variables of gentamicin were determined from steady-state peak (Cmax) and trough (Cmin) serum concentrations using individualized regimens in 88 patients. Dosages were determined in each patient using the method of Hull-Sarubbi, rule of eights, and the three new methods, and the resultant Cmax and Cmin values were calculated from dosages generated by each method. The daily doses and Cmax values derived with the Hull-Sarubbi, Thomson, and Reesor Nimmo methods were not significantly different (p > 0.05). The Hull-Sarubbi was the most precise (root mean squared prediction error 1.3) and least biased (mean prediction error -0.05) of the five methods in predicting target gentamicin serum peak concentrations (Cmax 6.5 mg/L). The Hull-Sarubbi (69%), Thomson (86%), and Reesor Nimmo (70%) methods yielded therapeutic Cmax (5-8 mg/L) in a significantly higher percentage of patients than did the rule of eights (32%) and DREM (35%), (p < 0.05). Therefore, if gentamicin serum concentrations are not available, the first three appear to be reasonable methods for initiating gentamicin dosage regimens, but the last two may not be desirable to use in a clinical setting. These conclusions are based on the assumption that patients are adults with stable renal function and relatively stable clinical conditions.
氨基糖苷类药物应用广泛，临床医生一直在寻找更新、更好的这些药物初始给药方法。最近，引入了三种新方法：汤姆森法、里瑟·尼莫法以及通过易于使用的乘数在肾病中给药法（DREM）。在将它们与不同程度肾功能患者的旧有传统给药方法进行比较时，在88例患者中使用个体化方案，根据稳态血清峰浓度（Cmax）和谷浓度（Cmin）测定庆大霉素的药代动力学变量。使用赫尔 - 萨鲁比法、八分法以及三种新方法为每位患者确定剂量，并根据每种方法产生的剂量计算所得的Cmax和Cmin值。用赫尔 - 萨鲁比法、汤姆森法和里瑟·尼莫法得出的每日剂量和Cmax值无显著差异（p>0.05）。在预测目标庆大霉素血清峰浓度（Cmax 6.5 mg/L）方面，赫尔 - 萨鲁比法是五种方法中最精确的（均方根预测误差为1.3）且偏差最小（平均预测误差为 -0.05）。与八分法（32%）和DREM（35%）相比，赫尔 - 萨鲁比法（69%）、汤姆森法（86%）和里瑟·尼莫法（70%）使患者达到治疗性Cmax（5 - 8 mg/L）的百分比显著更高（p<0.05）。因此，如果无法获得庆大霉素血清浓度，前三种方法似乎是启动庆大霉素给药方案的合理方法，但后两种方法在临床环境中可能不太适用。这些结论是基于患者为肾功能稳定且临床状况相对稳定的成年人这一假设得出的。
