Department of Pharmacy, Vancouver Hospital and Health Sciences Centre, 855 W. 12th Avenue, Vancouver, BC V5Z 1M9, Canada.
Clin Drug Investig. 1996 Aug;12(2):105-18. doi: 10.2165/00044011-199612020-00006.
The recent increase in the use of vancomycin has led to renewed interest in its pharmacokinetics, and, in particular, the importance of monitoring serum drug concentrations. A review of the literature and evaluation of pharmacokinetic data from Vancouver Hospital and Health Sciences Centre demonstrated that vancomycin meets the criteria necessary for serum drug concentration monitoring. These include the availability of a sensitive and specific assay, substantial interpatient and intrapatient variability in drug disposition, and evidence suggesting a correlation between vancomycin serum concentration and both efficacy and toxicity. A review of vancomycin disposition data for 371 consecutive treatment courses at this hospital revealed significant interpatient variability in drug clearance and volume of distribution. Accordingly, it would be difficult to accurately predict the change in serum concentration resulting from a given vancomycin dose. There appears to be less intrapatient variability in volume of distribution; however, serum elimination half-life tends to increase during treatment, necessitating an alteration in dose interval. Although convenient, physiological parameters to monitor serum creatinine concentration and bodyweight are not accurate predictors of drug clearance and volume of distribution. Serum concentration monitoring is also necessary to ensure that vancomycin concentrations are in excess of the minimum inhibitory concentration of the organism at all times during treatment. Although a causal relationship between vancomycin and toxicity has been difficult to prove, there is some evidence in the literature to support a relationship between high troughs and nephrotoxicity. In view of the available evidence, we do not believe that serum concentration monitoring should be totally abandoned. We have created empiric dosage guidelines and a decision-making algorithm for serum drug concentration monitoring that have streamlined the process of drug prescribing and monitoring at this institution.
近年来,万古霉素的应用不断增加,人们对其药代动力学重新产生了兴趣,尤其是监测血清药物浓度的重要性。对温哥华医院和健康科学中心的文献进行回顾和对药代动力学数据的评估表明,万古霉素符合进行血清药物浓度监测的标准。这些标准包括:有灵敏且特异的检测方法、药物处置中存在大量的个体间和个体内差异、有证据表明万古霉素血清浓度与疗效和毒性之间存在相关性。对该医院 371 例连续治疗疗程的万古霉素处置数据进行回顾,发现药物清除率和分布容积存在显著的个体间差异。因此,很难准确预测特定万古霉素剂量引起的血清浓度变化。分布容积的个体内差异似乎较小;然而,血清消除半衰期在治疗期间趋于增加,需要改变剂量间隔。尽管方便,但监测血清肌酐浓度和体重等生理参数并不能准确预测药物清除率和分布容积。为了确保在治疗期间始终使万古霉素浓度超过病原体的最低抑菌浓度,也需要进行血清浓度监测。虽然万古霉素与毒性之间的因果关系难以证明,但文献中有一些证据支持峰浓度与肾毒性之间存在关系。鉴于现有证据,我们认为不应该完全放弃血清浓度监测。我们制定了经验性剂量指南和血清药物浓度监测决策算法,简化了本机构的药物处方和监测流程。