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新型半乳糖单点法作为残余肝功能的一种测量方法:肝硬化患者头孢哌酮动力学实例

Novel galactose single point method as a measure of residual liver function: example of cefoperazone kinetics in patients with liver cirrhosis.

作者信息

Hu O Y, Tang H S, Chang C L

机构信息

School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC.

出版信息

J Clin Pharmacol. 1995 Mar;35(3):250-8. doi: 10.1002/j.1552-4604.1995.tb04055.x.

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 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)

摘要

一种新型、简单且临床实用的定量肝功能检测方法——半乳糖单点(GSP)法被开发出来,通过测量给予半乳糖(0.5 g/kg)1小时后的血半乳糖浓度来评估残余肝功能。该方法被应用于肝硬化患者头孢哌酮动力学的研究。为研究肝硬化对残余肝功能的影响以及残余肝功能与头孢哌酮药代动力学之间的相关性,给11名健康志愿者和12名肝硬化患者静脉注射1 g头孢哌酮。对每位志愿者和患者进行GSP法、半乳糖清除能力(GEC)检测和改良半乳糖清除能力(MGEC)检测以测量残余肝功能。用酶法测定半乳糖浓度。静脉注射头孢哌酮,给药后在适当时间间隔采集血样和尿样。所有血样和尿样均在-30℃保存直至进行高效液相色谱分析。在所有时间点,肝硬化患者的头孢哌酮血浆浓度均显著高于正常受试者。肝硬化患者的消除半衰期、肝清除率、平均驻留时间和肾清除率与健康志愿者有显著差异。两组的血浆蛋白结合率未改变。肝硬化患者的头孢哌酮尿排泄显著增加(正常男性为23.95±5.06%,肝硬化患者为51.09±11.50%)。肝清除率、尿排泄分数和总清除率与GSP、GEC和MGEC显著相关(P<0.001)。(摘要截短至250字)

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