The theophylline disposition after caffeine administration in liver cirrhosis: an index of liver function

Six blood samples covering a 24 hr post caffeine dosage were drawn in 8 healthy subjects and 18 patients with liver cirrhosis. Caffeine and theophylline concentration were assayed by gas-chromatography and fluorescent polarization immunoassay, respectively. In normals the maximum theophylline levels were found between 3 and 8 hrs (62.5% at 8 hrs) and ranged 50-420 ng/ml, whereas these levels in cirrhotic patients were noted between 3 and 12 hrs (61.1% at 8 hrs) and ranged 40-670 ng/ml. The largest difference in mean theophylline concentration between normals and cirrhotics was found at 6 hrs (348 +/- 103.7 ng/ml vs 217.1 +/- 140.8 ng/ml; p less than 0.02) and 24 hrs (101.6 +/- 57.3 ng/ml vs 172.2 +/- 119.6 ng/ml; p = 0.075) after caffeine dosing. Theophylline formation rate (theo6) differentiated controls from cirrhotics in the initial stage of the disease (Child-Pugh A), however it failed to discriminate between initial and late cirrhosis. In contrast, the ability of liver to remove theophylline (theo24) differentiated effectively these groups of patients. Theo6 to theo24 ratio was a valuable index of liver function, although its capacity to detect early cirrhosis was unsatisfactory.