Mahmoud Madiha, Abdel-Kader Rania, Hassanein Moataz, Saleh Samira, Botros Sanaa
Pharmacology Department, Theodor Bilharz Research Institute, Egypt.
Eur J Pharmacol. 2007 Aug 27;569(3):222-7. doi: 10.1016/j.ejphar.2007.04.061. Epub 2007 May 22.
In this study, 15 healthy volunteers and 96 patients with hepatitis C virus, classified according to Child-Pugh into 36 Child-A, 31 Child-B and 29 Child-C, were examined. All subjects ingested 600 mg antipyrine in the form of hard gelatinous capsules after overnight fasting. One milliliter of saliva was collected at 4 and 24 h after ingestion of antipyrine and analyzed using high-performance liquid chromatography. Blood samples were collected from all subjects for examination, using conventional liver function tests. The pharmacokinetic variables for antipyrine were determined using the two concentration time points selected. A cut-off value of 0.34 ml/min/kg was used to distinguish between cirrhotic and non-cirrhotic patients. Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase values were significantly higher with significantly lower antipyrine clearance in Child-A, B, and C patients than in normal volunteers. The total protein concentration was significantly lower in Child-B and C patients. Moreover, AST was significantly higher in Child-C patients and antipyrine clearance was lower in Child-B and C patients than in Child-A patients. Antipyrine clearance showed a significant negative correlation with Child-Pugh scores, total protein, the international normalization ratio of prothrombin time and globulin, and a positive correlation with albumin and albumin-to-globulin ratio. Unlike most of the conventional liver function tests, antipyrine clearance, which represents the intrinsic clearance capacity of the liver, measured using saliva, proved to be a sensitive marker of liver function. It was significantly impaired in the Child-Pugh group A patients with the least hepatic impairment. The international normalization ratio of prothrombin time was just as informative as antipyrine clearance in identifying minimal hepatic impairment.
在本研究中，对15名健康志愿者和96名丙型肝炎病毒患者进行了检查，这些患者根据Child-Pugh分级分为36名Child-A级、31名Child-B级和29名Child-C级。所有受试者在空腹过夜后服用600毫克硬明胶胶囊形式的安替比林。在摄入安替比林后4小时和24小时收集1毫升唾液，并使用高效液相色谱法进行分析。采集所有受试者的血样进行常规肝功能检查。利用选定的两个浓度时间点确定安替比林的药代动力学变量。使用0.34毫升/分钟/千克的临界值区分肝硬化和非肝硬化患者。与正常志愿者相比，Child-A级、B级和C级患者的丙氨酸转氨酶、天冬氨酸转氨酶和γ-谷氨酰转移酶值显著更高，而安替比林清除率显著更低。Child-B级和C级患者的总蛋白浓度显著更低。此外，Child-C级患者的AST显著更高，Child-B级和C级患者的安替比林清除率低于Child-A级患者。安替比林清除率与Child-Pugh评分、总蛋白、凝血酶原时间国际标准化比值和球蛋白呈显著负相关，与白蛋白和白蛋白与球蛋白比值呈正相关。与大多数传统肝功能检查不同，使用唾液测量的代表肝脏固有清除能力的安替比林清除率被证明是肝功能的敏感指标。在肝损伤最轻的Child-Pugh A组患者中，其显著受损。凝血酶原时间国际标准化比值在识别轻度肝损伤方面与安替比林清除率同样具有信息量。
