Antipyrine kinetics in liver disease and liver transplantation

Abstract

Antipyrine kinetics were studied in seven normal subjects, 10 patients with liver disease, and 13 clinically stable patients who received a liver transplant. Five patients were studied both before and after liver transplantation. Antipyrine concentrations in saliva after oral dosing were measured by HPLC. The antipyrine t 1/2 was significantly longer (P < 0.05) in patients with liver disease than in patients undergoing liver transplantation and normal subjects. Antipyrine clearance was not significantly different between patients undergoing liver transplantation and normal subjects, but it was significantly reduced (P < 0.05) in patients with liver disease. In five patients who were studied before and after liver transplantation, there was a significant (P < 0.05) increase in the antipyrine clearance and a marked reduction in its t 1/2 after liver transplantation. These results indicate that liver transplantation improves the drug metabolizing ability of patients with liver disease and that the oxidative metabolizing capacity of the liver in clinically stable patients after liver transplantation is similar to that of normal subjects.Liver disease alters the absorption and disposition of a variety of drugs. 1,2 Liver transplantation is considered to be an effective therapeutic option in certain liver diseases such as biliary atresia, sclerosing cholangitis, alcoholic cirrhosis, and primary biliary cirrhosis and in certain metabolic disorders such as α 1 -antitrypsin deficiency. 3,4 After liver transplantation, patients receive a number of drugs including immunosuppressants, antihypertensives, antivirals, antifungals, and antibiotics. However, very little is known about the drug metabolizing capacity in patients after successful liver transplantation.Our primary objective was to determine the oxidative metabolizing capacity of the liver in patients after liver transplantation and to compare this with normal subjects and patients with liver disease. We also compared oxidative drug metabolizing capacity before and after liver transplantation in the same patient by determining antipyrine kinetic parameters. METHODSAll participants gave informed, written consent before entering the study. Participants were nonsmokers and refrained from alcohol consumption for at least 1 week before and during the study. Biochemical profiles including albumin, total protein, bilirubin (total and direct), SGOT, SGPT, γ-guanosine triphosphate (γ-GTP), and alkaline phosphatase levels were determined before the study. Studies were conducted in seven normal subjects (four men and three women), 10 patients with liver disease (seven men and three women), and 13 patients (eight men and five women) who were clinically stable (total bilirubin <2.0 mg/dl) after liver transplantation. In all of the latter patients the study was conducted 1 to 2 months after transplantation, except in one patient who was studied 7 months after transplantation. Before drug dosing blank saliva and urine samples were collected from all participants. After an o...

Improved dialytic removal of protein-bound uraemic toxins with use of albumin binding competitors: an in vitro human whole blood study

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Morphological Regeneration and Hepatic Functional Mass after Right Hemihepatectomy

“…Mehta et al[ 22] reported the antipyrine kinetics in liver disease and liver transplantation. Their results indicate that liver transplantation improves the drug metabolizing ability of patients with liver disease and that the oxidative metabolizing capacity of the liver in clinically stable patients after liver transplantation is similar to that of normal subjects, showing the eligibility of antipyrine clearance test for the patients underwent hepatactomy.…”

Effect of Age and Postoperative Time on Cytochrome P450 Enzyme Activity Following Liver Transplantation

“…The use of metabolic probes to quantitate the phenotypic expression of CYPs is a widely used approach to study changes in drug metabolism. An early study by our group demonstrated that antipyrine clearance normalized rapidly after OLTx 5 . An extension of these studies included multiple probes for CYP activity.…”

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