A novel, simple, clinically useful quantitative liver function test, called the
galactose single point (GSP) method, was developed to assess residual liver function by measuring
galactose blood concentration 1 hour after
galactose was administered (0.5 g/kg). This method was applied to the study of
cefoperazone kinetics in patients with
hepatic cirrhosis. To study the influence of
hepatic cirrhosis on the residual liver function and the correlation between the residual liver function and the pharmacokinetics of
cefoperazone, a dose of 1 g of
cefoperazone was administered to 11 healthy volunteers and 12 patients with
liver cirrhosis. The GSP method, the
galactose elimination capacity (GEC) test, and the modified
galactose elimination capacity (MGEC) test were done for each volunteer and patient to measure residual liver function. The
galactose concentrations were determined enzymatically.
Cefoperazone was administered intravenously, and blood and urine samples were collected at appropriate intervals after
drug administration. All blood and urine samples were stored at -30 degrees C until high-performance liquid chromatography analysis.
Cefoperazone plasma concentrations were much higher in
cirrhosis patients than in normal subjects at all times. The elimination half-life, hepatic clearance, mean residence time, and renal clearance of
cirrhosis patients differed significantly from those of healthy volunteers. The
plasma protein binding was unaltered in both groups. Urinary excretion of
cefoperazone was significantly increased in
cirrhosis patients (23.95 +/- 5.06% for normal men and 51.09 +/- 11.50% in
cirrhosis patients). Hepatic clearance, fraction excreted in urine, and total clearance significantly correlated with GSP, GEC, and MGEC (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)