Caffeine clearance by two point analysis: a measure of liver function in chronic liver disease

This study attempted to compare the pharmacokinetic parameters of caffeine in patients with chronic liver disease and in normal subjects and to define the two sampling times which are suitable for determining caffeine clearance in these patients. Ten decompensated and eight compensated cirrhotic patients, and nine patients with chronic hepatitis were given a 3.5 mg/kg single oral dose of caffeine, followed by measurement of serum caffeine concentrations at 0, 30, 60, 90 minutes and 3, 5, 10, 24 and 36 hours using the HPLC technique. Caffeine clearance and its elimination rate constant in the decompensated cirrhotic patients were significantly lower than those in the compensated cirrhotic patients and much lower than in normal subjects (p > 0.01). Caffeine clearance in chronic hepatitis patients was also significantly lower than in normal subjects. The volumes of distribution of caffeine in compensated and decompensated cirrhotic patients and normal subjects were significantly different. There was also a significant difference between normal subjects and the chronic hepatitis group. Serum caffeine clearance showed a good correlation with Child Pugh's score at r = -0.788. Two sampling times within 10 to 24 hours after oral dose of caffeine served as the best sampling points for determination of caffeine clearance by the simple equation; Cl = kel approximately Vd (Vd is a fixed value in each group). It was clearly shown that caffeine clearance, calculated by two point analysis, would be a simple and useful method for measuring liver function in chronic liver disease.