老年人与年轻人相比游离苯妥英的“表观清除率”。

The 'apparent clearance' of free phenytoin in elderly vs. younger adults.

机构信息

Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand.

出版信息

Br J Clin Pharmacol. 2010 Jul;70(1):132-8. doi: 10.1111/j.1365-2125.2010.03673.x.

DOI:10.1111/j.1365-2125.2010.03673.x

PMID:20642556

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2909816/

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

The clearance of many drugs is reduced in the elderly, but the data regarding phenytoin are conflicting. Most studies have estimated phenytoin metabolic clearance using total drug concentrations (bound plus unbound), which may be confounded by protein binding effects. Free phenytoin concentrations are independent of protein binding and should more accurately reflect true metabolic clearance changes in elderly patients.

WHAT THIS STUDY ADDS

The two studies reported in this paper suggest a trend towards reduced free phenytoin 'apparent clearance' in the elderly, although statistically significant results were not found. Other published studies have largely found similar trends, suggesting an age effect.

AIMS

To test the hypothesis that the 'apparent clearance' of free phenytoin is reduced in elderly patients.

METHODS

Two separate studies were conducted comparing free phenytoin 'apparent clearance' in elderly vs. younger adults. The first study was a retrospective analysis of free phenytoin concentrations measured at Christchurch Hospital from 1997 to 2006. In the second study free phenytoin concentrations were measured prospectively in ambulatory subjects who were taking phenytoin regularly.

RESULTS

In the retrospective study (n= 29), free phenytoin 'apparent clearance' was 0.27 +/- 0.04 l kg(-1) day(-1) (95% CI 0.19, 0.34) in the elderly cohort vs. 0.37 +/- 0.06 l kg(-1) day(-1) (95% CI 0.22, 0.52) in younger adults, but the difference was not statistically significant. In the prospective study, free phenytoin 'apparent clearance' showed a non-significant trend to being reduced in the elderly patients (0.12 +/- 0.02 l kg(-1) day(-1), 95% CI 0.07, 0.17) compared with the younger cohort (0.18 +/- 0.07 l kg(-1) day(-1), 95% CI 0.09, 0.26) in those not taking interacting drugs (n= 21).

CONCLUSIONS

This research does not prove the hypothesis that the 'apparent clearance' of free phenytoin is reduced in the elderly. However, the trends found in these two studies are supported by trends in the same direction in other published studies, suggesting an age effect.

摘要

已知关于这一主题的情况

许多药物在老年人中的清除率降低，但有关苯妥英的数据存在冲突。大多数研究使用总药物浓度（结合和未结合）来估计苯妥英的代谢清除率，这可能会受到蛋白结合效应的影响。游离苯妥英浓度与蛋白结合无关，应更准确地反映老年患者真正的代谢清除率变化。

本研究增加了什么

本文报道的两项研究表明，老年患者游离苯妥英“表观清除率”呈下降趋势，但未发现统计学意义上的结果。其他已发表的研究也发现了类似的趋势，表明存在年龄效应。

目的

测试游离苯妥英“表观清除率”在老年患者中降低的假设。

方法

进行了两项独立的研究，比较了老年患者和年轻患者的游离苯妥英“表观清除率”。第一项研究是对 1997 年至 2006 年在克赖斯特彻奇医院测量的游离苯妥英浓度进行的回顾性分析。第二项研究是前瞻性研究，测量了定期服用苯妥英的门诊患者的游离苯妥英浓度。

结果

在回顾性研究（n=29）中，老年组游离苯妥英“表观清除率”为 0.27 +/- 0.04 l kg(-1) day(-1)（95%CI 0.19，0.34），年轻组为 0.37 +/- 0.06 l kg(-1) day(-1)（95%CI 0.22，0.52），但差异无统计学意义。在前瞻性研究中，未服用相互作用药物的老年患者（n=21）的游离苯妥英“表观清除率”呈下降趋势，但无统计学意义（0.12 +/- 0.02 l kg(-1) day(-1)，95%CI 0.07，0.17），与年轻组（0.18 +/- 0.07 l kg(-1) day(-1)，95%CI 0.09，0.26）相比。