Martin-Facklam Meret, Rengelshausen Jens, Tayrouz Yorki, Ketabi-Kiyanvash Nahal, Lindenmaier Heike, Schneider Verena, Bergk Verena, Haefeli Walter E
Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.
Eur J Clin Pharmacol. 2005 Jan;60(11):807-11. doi: 10.1007/s00228-004-0852-y. Epub 2004 Dec 14.
An important information source for pharmacotherapy in populations at risk is drug labelling. We compared the recommendations for patients with renal insufficiency included in German drug labellings with evidence from the literature.
From the 120 drugs with the highest turnover in a large university hospital, all drugs with pharmacokinetics independent of renal function (n=48) and those with substantial accumulation in renal failure (n=28) were identified. For both groups of compounds, pharmacokinetic and pharmacodynamic aspects relevant for dose individualisation in those with renal insufficiency were extracted from the literature and compared with the information given in the German drug labelling.
Over half of the labellings (15 of 26) of non-accumulating drugs without renal adverse drug reactions contained no dose recommendation for patients with renal insufficiency. The labelling of nephrotoxic compounds that do not accumulate included more frequently a recommendation to adapt the dose or to monitor than the labelling of drugs without nephrotoxic potential (15 of 22 versus 5 of 26, P=0.002). For over half of accumulating drugs (16 of 28), the dose given in the labelling depends primarily on creatinine clearance. The ratio between the labelling dose and the dose based on the pharmacokinetic concept to achieve identical plasma concentrations (Q0 concept) differed widely (0.4-2).
When renal failure had no impact on dosing, information was often missing. Such information is however important to differentiate, whether no dose adaptation is necessary or no information is available. If dose adjustment is required, application of a uniform concept is desirable.
药物标签是高危人群药物治疗的重要信息来源。我们将德国药物标签中针对肾功能不全患者的建议与文献证据进行了比较。
在一家大型大学医院中，从销售额最高的120种药物中，识别出所有药代动力学与肾功能无关的药物（n = 48）以及那些在肾衰竭时会大量蓄积的药物（n = 28）。对于这两组化合物，从文献中提取了与肾功能不全患者剂量个体化相关的药代动力学和药效学方面的信息，并与德国药物标签中给出的信息进行比较。
在无肾不良药物反应的非蓄积性药物标签中，超过一半（26种中的15种）没有针对肾功能不全患者的剂量建议。与无肾毒性潜在风险的药物标签相比，不蓄积的肾毒性化合物标签更频繁地包含调整剂量或监测的建议（22种中的15种与26种中的5种，P = 0.002）。对于超过一半的蓄积性药物（28种中的16种），标签中给出的剂量主要取决于肌酐清除率。标签剂量与基于药代动力学概念以达到相同血浆浓度的剂量（Q0概念）之间的比值差异很大（0.4 - 2）。
当肾衰竭对给药无影响时，信息常常缺失。然而，这种信息对于区分是无需调整剂量还是没有可用信息很重要。如果需要调整剂量，采用统一的概念是可取的。
