Pharmacokinetics and metabolism of theophylline in patients with liver diseases.

In patients with acute hepatitis, cholestasis, and compensated or decompensated liver cirrhosis the kinetics and urinary excretion of theophylline and metabolites were investigated following intravenous administration (193 mg). Significant decreases of plasma clearance and a prolongation of the plasma elimination half-life were found only in cases with decompensated liver cirrhosis and to a lesser extent in cases of acute hepatitis. The metabolite pattern in urine was changed in all disease groups compared to controls, i.e., increased excretion of 1-methyl uric acid and a concomitant decrease of 1,3-dimethyl uric acid and particularly of 3-methylxanthine. These results allow the following conclusions. In liver disease the 1-demethylation of theophylline is inhibited; this inhibition appears to be compensated by a shift towards 1-methyl uric acid formation. The monitoring of plasma levels of theophylline is indicated, especially in therapy of patients wtih decompensated liver cirrhosis.