AGE AS AN INFLUENCING FACTOR OF THE DOSE- RESPONSE RELATIONSHIP

Drug therapy in the elderly requires careful individualization of the dosage. Whether dose adjustment is due to altered pharmacokinetic or d ue to altered pharmacodynamic is a matter of experimental evidence whi ch can be found by performing studies with simultaneous measurements o f concentration and effect over time. The kinetic of drugs in the elde rly can be characterized by an altered volume of distribution, an alte red protein binding, an impaired metabolism and renal excretion. There is a wide interindividual variation of the alterations which are furt her influenced by environmental factors such as smoking and nutrition. In generalization of the results it can be assumed that the concentra tion of drugs is elevated in the elderly and that the excretion will b e 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 muc h 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 find ing is explained on a pharmacodynamic basis (e.g., enhanced receptor s ensitivity, 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 th at 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 c ase of new symptom side-effects of drugs should be considered as the u nderlying cause.