Novel Galactose Single Point Method as a Measure of Residual Liver Function: Example of Cefoperazone Kinetics in Patients with Liver Cirrhosis

Oliver Yoa‐Pu Hu, Hung‐Shang ‐S Tang, Ching‐Ling ‐L Chang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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°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). These results suggest that (1) cefoperazone kinetics was significantly altered in patients with cirrhosis; and (2) the GSP method can predict the cefoperazone clearances in patients with liver dysfunction. 1995 American College of Clinical Pharmacology

Original languageEnglish
Pages (from-to)250-258
Number of pages9
JournalThe Journal of Clinical Pharmacology
Volume35
Issue number3
DOIs
Publication statusPublished - Jan 1 1995
Externally publishedYes

Fingerprint

Cefoperazone
Galactose
Liver Cirrhosis
Liver
Fibrosis
Urine
Healthy Volunteers
Clinical Pharmacology
Liver Function Tests
Protein Binding
Liquid Chromatography
Half-Life
Liver Diseases
Blood Proteins
Volunteers
Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Novel Galactose Single Point Method as a Measure of Residual Liver Function : Example of Cefoperazone Kinetics in Patients with Liver Cirrhosis. / Hu, Oliver Yoa‐Pu; Tang, Hung‐Shang ‐S; Chang, Ching‐Ling ‐L.

In: The Journal of Clinical Pharmacology, Vol. 35, No. 3, 01.01.1995, p. 250-258.

Research output: Contribution to journalArticle

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abstract = "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°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). These results suggest that (1) cefoperazone kinetics was significantly altered in patients with cirrhosis; and (2) the GSP method can predict the cefoperazone clearances in patients with liver dysfunction. 1995 American College of Clinical Pharmacology",
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