Pryka R D, Rodvold K A, Erdman S M
College of Pharmacy, University of Toledo, Ohio.
Clin Pharmacokinet. 1991 Jun;20(6):463-76. doi: 10.2165/00003088-199120060-00003.
The resurgence of the use of and interest in vancomycin, in conjunction with the high degree of interpatient variability in its pharmacokinetic profile, has prompted the development of many and varied dosing methods. Several dosing nomograms have been proposed and evaluated, methods which are useful for initial dosing but do not allow for individualisation of dosage. Given these constraints, several investigators have attempted to apply conventional least-squares regression techniques and, more recently, Bayesian methodologies using either 1- or 2-compartment pharmacokinetic models. Comparative information evaluating algorithmic methods demonstrates that those of Moellering and Lake offer the least biased and most precise predictions of vancomycin dosage. Patient individualisation using conventional least-squares methodology offers some improvement over nomogram-based methods, both in predictive performance and in dosage adjustment once serum concentration data are available. Overall, the latest data indicate that regimens which incorporate Bayesian principles tend to give better results than nomogram-based or conventional least-squares dosing methods for this drug. Despite the advances in methods for dosing vancomycin, several questions remain to be answered. A lack of convincing evidence of a correlation between serum concentrations and therapeutic outcome has prompted debate over the need for serum concentration monitoring and, if it is needed, over which patient population would most benefit. Secondly, little comparative information is currently available as to the dosing of vancomycin in paediatric and neonatal patient populations. Several nomograms for initial dosing have been proposed, but only 2 have been subject to subsequent testing. Finally, information regarding cost-effectiveness and the quality of patient outcome is lacking from the current literature.
万古霉素使用的再度兴起以及人们对其兴趣的增加,再加上患者间药代动力学特征的高度变异性,促使了多种给药方法的发展。已经提出并评估了几种给药剂量图表,这些方法对初始给药有用,但不允许剂量个体化。鉴于这些限制,一些研究人员试图应用传统的最小二乘回归技术,以及最近使用单室或双室药代动力学模型的贝叶斯方法。评估算法方法的比较信息表明,Moellering和Lake的方法对万古霉素剂量的预测偏差最小且最精确。使用传统最小二乘法进行患者个体化,在预测性能以及血清浓度数据可用时的剂量调整方面,比基于剂量图表的方法有所改进。总体而言,最新数据表明,对于这种药物,纳入贝叶斯原理的给药方案往往比基于剂量图表或传统最小二乘给药方法产生更好的结果。尽管万古霉素给药方法取得了进展,但仍有几个问题有待回答。缺乏血清浓度与治疗结果之间相关性的令人信服的证据,引发了关于是否需要进行血清浓度监测的争论,如果需要监测,哪些患者群体将最受益。其次,目前关于儿科和新生儿患者群体中万古霉素给药的比较信息很少。已经提出了几种初始给药的剂量图表,但只有两种经过了后续测试。最后,当前文献缺乏关于成本效益和患者治疗结果质量的信息。