The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease.

1. Serum and salivary concentrations of caffeine (1,3,7-trimethylxanthine) and its dimethylxanthine metabolites were measured in 10 healthy control subjects and in 19 patients with cirrhosis, for up to 96 h following a 400 mg oral caffeine load. 2. Serum and salivary caffeine concentrations correlated significantly (r = 0.954; P less than 0.001) and no significant differences were observed in the pharmacokinetic data derived from the respective concentration-time curves. 3. In the control subjects, basal salivary caffeine concentrations did not exceed 0.4 mg l-1. The median (range) basal salivary caffeine concentrations in patients with compensated cirrhosis (n = 10), 0.2 (0-0.7) mg l-1 and decompensated cirrhosis (n = 9), 0.7 (0-5.8) mg l-1, were not significantly different from control values, although three patients with decompensated cirrhosis had basal salivary caffeine values above 2.0 mg l-1. 4. In the patients with compensated cirrhosis, the median peak salivary caffeine concentration, 10.9 (8.2-16.5) mg l-1 was significantly greater than in controls, 7.1 (4.7-11.8) mg l-1 (P less than 0.01) and the median apparent volume of distribution was significantly reduced, 0.38 (0.19-0.49) vs 0.41 (0.23-0.63) l kg-1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)