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Updated: Jul 13, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Antipyrine clearance in comparison to conventional liver function tests in hepatitis C virus patients
Madiha Mahmoud1, Rania Abdel-Kader, Moataz Hassanein
1Pharmacology Department, Theodor Bilharz Research Institute, Egypt.
Insights
Antipyrine clearance measured in saliva is a sensitive marker for liver function in hepatitis C patients. This test effectively identifies even minimal hepatic impairment, correlating well with liver disease severity.
Area of Science:
- Hepatology
- Pharmacokinetics
- Biomarker Discovery
Background:
- Hepatitis C virus (HCV) infection leads to liver cirrhosis, necessitating accurate assessment of liver function.
- Conventional liver function tests (LFTs) have limitations in detecting early-stage hepatic impairment.
Purpose of the Study:
- To evaluate antipyrine clearance, measured in saliva, as a sensitive biomarker for liver function in patients with HCV.
- To compare the efficacy of antipyrine clearance with conventional LFTs and Child-Pugh scores in assessing hepatic function.
Main Methods:
- 15 healthy volunteers and 96 HCV patients (Child-A, B, C) ingested 600 mg antipyrine.
- Saliva samples were collected at 4 and 24 hours post-ingestion for high-performance liquid chromatography analysis.
- Conventional LFTs and Child-Pugh scores were assessed concurrently.
Main Results:
- Antipyrine clearance was significantly reduced in all Child-Pugh groups (A, B, C) compared to healthy volunteers.
- Saliva-based antipyrine clearance demonstrated a strong negative correlation with Child-Pugh scores and other established markers.
- Antipyrine clearance proved sensitive in detecting impairment even in Child-A patients, indicating minimal hepatic dysfunction.
Conclusions:
- Saliva-based antipyrine clearance is a sensitive, non-invasive biomarker for assessing liver function in HCV patients.
- This method effectively identifies minimal hepatic impairment, offering an advantage over some conventional LFTs.
- Antipyrine clearance provides valuable insights into the liver's intrinsic clearance capacity, aiding in disease management.
Abstract:
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.
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