Die Elimination von Koffein bei Lebererkrankungen

Summary

Caffeine, a 1,3,7-trimethylxanthine, is eliminated predominantly by metabolism (demethylation and oxidation) in the liver. In patients with liver diseases the caffeine elimination can be impaired leading to unexpected side effects. We therefore investigated the plasma concentrations of caffeine in patients with chronic liver disease 19–24 hrs after the last caffeine ingestion. Furthermore a group of patients with liver cirrhosis received 200 mg caffeine iv. The plasma concentrations determined by gas chromatography (HP 5711) with nitrogen selective detection were followed up to 48 hrs later. Half life, total clearance and volume of distribution were calculated (HP 41 C). In 34 patients without liver disease caffeine plasma concentrations were 0.13 ± 0.24 µig/ml and in patients with chronic liver disease (n = 8) 0.13 ± 0.14 µg/ml. In patients with fatty liver (n = 13) and especially with cirrhosis of the liver (n = 21) spontaneous caffeine plasma concentrations were significantly (p < 0.005) higher than in the control subjects (fatty liver 0.59 ± 0.52 µg/ml; inactive cirrhosis (n = 9) 0.74 ± 1.27 µg/ml, active cirrhosis (n = 12) 2.84 ± 2.49 µig/m1). Half life in healthy volunteers (n = 9) ranged from 1.7 to 5.3 hrs, clearance from 51 to 513 ml/min. In the whole group of patients with cirrhosis of the liver (n = 10) half life was prolonged 6 fold and clearance was reduced to a fifth of the normal value. Caffeine clearance was impaired especially in patients with an advanced state of liver disease: in active cirrhosis (n = 5) clearance of caffeine was diminished on average to 8 % of normal. The volume of distribution was unchanged (healthy volunteers: 39 ± 16 1, liver cirrhosis 41 ± 22 1). Our results show a reduced elimination of caffeine in patients with chronic liver disease. An accumulation of caffeine in these patients is therefore to be expected. In advanced liver diseases such as active cirrhosis of the liver caffeine should be avoided if possible, in order to prevent clinically relevant side effects. Since caffeine clearance is related to the degree of liver impairment this substance can be used to demonstrate disturbances of liver drug metabolism.

Zusammenfassung

Die Elimination von Koffein ist bei chronischen Lebererkrankungen deutlich verzögert. Um eine Kumulation und ein damit verbundenes Auftreten von Unverträglichkeiten bzw. Nebenwirkungen zu vermeiden, sollte der Genuß von Koffein besonders bei fortgeschrittenen Lebererkrankungen nicht erlaubt werden. Auf Grund der guten Korrelation zwischen der Koffein-Clearance und dem Schweregrad der Lebererkrankung scheint Koffein eine geeignete Substanz für die Beurteilurig der Aktivität des mikrosomalen Enzymsystems der Leber zu sein.