Einfluß des Alters auf die hepatische Elimination von Koffein, Hexobarbital und Lidocain in einem internistischen Patientenkollektiv

Summary The liver, like other organs, undergoes age dependent atrophy. Physiological functions are not critically diminished, whereas oxidative drug metabolism is impaired for many substrates. This may be the reason for a higher incidence of adverse drug reactions in the elderly. We studied the influence of age on the hepatic elimina­ tion of two low clearance model-substrates of the oxidative metabolism, hexo­ barbital (cytochrome P 450) and caffeine (cytochrome P 448), and of lidocaine, a high clearance drug, in patients without liver disease and after exclusion of inter­ fering factors (smoking, inducing drugs and oral contraceptives). Plasma concentra­ tions of the three drugs were determined by gaschromatography and pharmaco­ kinetic parameters were calculated from a one compartment open model (caffeine, hexobarbital) or in steady state (lidocaine). Caffeine clearance decreased significantly with age (15-88 years) with corresponding changes in halflife, whereas volume of distribution was not influenced (Clearance (mllmin) = 94.16 - 0.56 x years, r = 0.52, n = 61). Less pronounced, but also significant changes for the 12 h plasma-concen­ tration of hexobarbital and the lidocaine clearance could be demonstrated. How­ ever, the effect of liver disease completely overrules the influence of age on caffeine and hexobarbital elimination and the same holds true for pump failure of the heart in the case of lidocaine. We conclude, that in comparison with age dependent im­ pairment of oxidative liver metabolism other clinical conditions are of greater importance for the adjustment of a dosage regimen in pharmacotherapy of the elderly. Nevertheless appropriate dose reduction can be recommended in general in old age.