Novel galactose single point method as a measure of residual liver function: example of cefoperazone kinetics in patients with liver cirrhosis.
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)
Hu
O Y
OY
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC.
Tang
H S
HS
Chang
C L
CL
D000328:Adult; D002438:Cefoperazone / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005690:Galactose / Q000032:analysis*; D005693:Galactosemias / Q000175:diagnosis / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate
D002438:Cefoperazone; D005690:Galactose