Leader W G, Chandler M H, Castiglia M
Department of Clinical Pharmacy, School of Pharmacy, West Virginia, University, Morgantown, USA.
Clin Pharmacokinet. 1995 Apr;28(4):327-42. doi: 10.2165/00003088-199528040-00005.
Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and concentration-response relationships. No definitive data exist that correlate vancomycin serum concentrations with clinical outcomes. However, inconsistencies in sampling times for peak serum concentrations and differences in infusion times make interpreting vancomycin serum concentrations difficult. Furthermore, the evidence implicating vancomycin as a cause of oto- or nephrotoxicity is circumstantial, and these adverse effects may occur only in high-risk populations. Owing to the variability in its dose-serum concentration relationship and multicompartmental pharmacokinetics, several methodologies have been developed for instituting and adjusting vancomycin dosages. Nomograms rely on a fixed volume of distribution and the relationship between vancomycin clearance and creatinine clearance. Since both of these factors may be altered in certain populations, dosage methodologies (both traditional and Bayesian) that use population- or patient-specific pharmacokinetic data perform better than standard nomograms for initiating vancomycin therapy. Controversy still exists as to whether a 1- or a 2-compartment model is more appropriate for making dosage adjustments; however, steady-state rather than non-steady-state vancomycin serum concentrations should be used for dosage adjustments. Certain pathophysiological states such as age, bodyweight and renal function contribute to altered pharmacokinetics and may alter the design of the dosage regimen. Since no definitive relationship exists between vancomycin serum concentrations and either clinical outcome or adverse effects, considerable controversy surrounds the utility of monitoring serum vancomycin concentrations. Therefore, routine vancomycin serum concentration monitoring may be warranted only in specific populations, such as patients receiving concurrent aminoglycoside therapy or those receiving higher than usual dosages of vancomycin, patients undergoing haemodialysis and patients with rapidly changing renal function.
在过去十年中，人们对万古霉素的兴趣再度兴起，这催生了大量关于万古霉素药代动力学、剂量选择及其浓度-反应关系的数据。目前尚无明确数据表明万古霉素血清浓度与临床结局之间存在关联。然而，血清浓度峰值的采样时间不一致以及输注时间的差异，使得解读万古霉素血清浓度变得困难。此外，将万古霉素视为耳毒性或肾毒性病因的证据只是间接的，而且这些不良反应可能仅发生在高危人群中。由于万古霉素剂量-血清浓度关系的变异性以及多房室药代动力学特性，已开发出多种确定和调整万古霉素剂量的方法。列线图依赖于固定的分布容积以及万古霉素清除率与肌酐清除率之间的关系。由于这两个因素在某些人群中可能会发生改变，因此使用群体或患者特异性药代动力学数据的剂量计算方法（传统方法和贝叶斯方法）在启动万古霉素治疗时比标准列线图表现更好。对于采用一室模型还是二室模型进行剂量调整更为合适，目前仍存在争议；然而，剂量调整应使用万古霉素的稳态血清浓度而非非稳态血清浓度。某些病理生理状态，如年龄、体重和肾功能，会导致药代动力学改变，并可能影响给药方案的设计。由于万古霉素血清浓度与临床结局或不良反应之间不存在明确关系，因此关于监测血清万古霉素浓度的实用性存在相当大的争议。因此，仅在特定人群中可能需要进行常规万古霉素血清浓度监测，例如同时接受氨基糖苷类治疗的患者、接受高于常规剂量万古霉素治疗的患者、接受血液透析的患者以及肾功能快速变化的患者。
