Gundert-Remy U
Abteilung für Klinische Pharmakologie, Zentrum für Pharmakologie, Göttingen.
Z Gerontol Geriatr. 1995 Nov-Dec;28(6):408-14.
Drug therapy in the elderly requires careful individualization of the dosage. Whether dose adjustment is due to altered pharmacokinetic or due to altered pharmacodynamic is a matter of experimental evidence which can be found by performing studies with simultaneous measurements of concentration and effect over time. The kinetic of drugs in the elderly can be characterized by an altered volume of distribution, an altered protein binding, an impaired metabolism and renal excretion. There is a wide interindividual variation of the alterations which are further influenced by environmental factors such as smoking and nutrition. In generalization of the results it can be assumed that the concentration of drugs is elevated in the elderly and that the excretion will be prolonged. Hence, it is safe to reduce the dose in the elderly. The influence of age on factors which determine the effect of drugs is much less investigated than the factors influencing the pharmacokinetic. With respect to side-effects, it seems that the elderly population is a population at special risk. However, it is unclear whether this finding is explained on a pharmacodynamic basis (e.g., enhanced receptor sensitivity, impaired homeostatic mechanisms), as analyses are lacking in investigating the relationship between concentration and effect. As there is no evidence besides a special situation with betablockers that aged patients require higher doses than younger ones, it is wise to use doses at the lower range for the treatment of aged patients. In case of new symptom side-effects of drugs should be considered as the underlying cause.
老年人的药物治疗需要仔细进行剂量个体化。剂量调整是由于药代动力学改变还是药效动力学改变,这需要实验证据来确定,可通过进行同时测量一段时间内药物浓度和效应的研究来找到相关证据。老年人药物的动力学特点可能表现为分布容积改变、蛋白结合改变、代谢及肾排泄受损。这些改变存在很大的个体间差异,还会受到吸烟和营养等环境因素的进一步影响。概括研究结果可以认为,老年人的药物浓度会升高,排泄时间会延长。因此,对老年人减少剂量是安全的。与影响药代动力学的因素相比,年龄对决定药物效应的因素的影响研究得要少得多。就副作用而言,老年人群似乎是一个特殊风险群体。然而,由于缺乏对浓度与效应之间关系的研究分析,尚不清楚这一发现是否能用药效动力学基础(如受体敏感性增强、体内平衡机制受损)来解释。除了β受体阻滞剂的特殊情况外,没有证据表明老年患者需要比年轻患者更高的剂量,因此明智的做法是在治疗老年患者时使用较低范围的剂量。如果出现新症状,应考虑药物副作用是潜在原因。