Serial antipyrine clearance studies detect altered hepatic metabolic function during spontaneous and interferon-induced changes in chronic hepatitis B disease activity

Farrell, Geoffrey C.

doi:10.1002/hep.1840100212

Cited by 29 publications

(7 citation statements)

References 41 publications

(43 reference statements)

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“…These results are similar to those reported by Monroe et al s for the aminopyrine breath test, and suggest that repeated TMO testing could be an alternative to the frequent liver biopsies performed in monitoring the progress from CAH or CPH to CAHC, and that TMO testing could possibly be used to monitor the effects of treatment. Indeed, it has been shown, by Williams and Farrell,6 that repeated use of the antipyrine test and comparison with the initial baseline data improves its sensitivity and is useful for monitoring the patient's response to interferon therapy. The simplicity of TMO testing would make it very useful for such repeated testing.…”

Section: Discussionmentioning

confidence: 97%

Clinical significance of the trimethadione tolerance test in chronic hepatitis: A useful indicator of hepatic drug metabolizing capacity

Abei

Tanaka

et al. 1995

J Gastroenterol

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Trimethadione (TMO) was chosen as an indicator of quantitative hepatic microsomal function, and its pharmacokinetics were studied in 52 patients with chronic hepatitis. Findings in these patients were compared with those for 26 healthy subjects and 13 patients with renal failure. Patients with chronic hepatitis, but not those with renal failure, showed significant reduction in clearance (CL) and prolongation of half-life (t1/2), and the extent of abnormalities was found to reflect the severity of histologic changes in liver tissue. The serum dimethadione (DMO)/TMO ratio 4 h after the administration of TMO altered in parallel with the CL and t1/2 of TMO, and abnormalities in this simple ratio were also related to the histologic severity of changes in the liver tissue. A low DMO/TMO ratio (< 0.4) was associated with advanced histologic changes (chronic active hepatitis with bridging or chronic active hepatitis with cirrhosis), whereas a high DMO/TMO ratio (> 0.4) was associated with mild histologic changes (chronic persistent hepatitis or chronic active hepatitis) (sensitivity, 0.81; specificity, 0.86). These results indicate that the DMO/TMO ratio, which can be obtained from a single blood sampling, reflects the histologic severity of changes in tissue liver, and that the TMO tolerance test is a useful indicator of quantitative liver function.

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Section: Discussionmentioning

confidence: 97%

Clinical significance of the trimethadione tolerance test in chronic hepatitis: A useful indicator of hepatic drug metabolizing capacity

Abei

Tanaka

et al. 1995

J Gastroenterol

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“…Recently, Grieco et ul.""' and Robertz-Correspondence: Dr Antonio Grieco, Department of Internal Medicine and Geriatrics, Catholic University of the Sacred Accepted for publication 28 November 1997.…”

Section: Introductionmentioning

confidence: 99%

Antipyrine clearance in chronic and neoplastic liver diseases: A study of 518 patients

Greco

Castellano

Matera

et al. 1998

J of Gastro and Hepatol

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Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve of the liver. It is well known that metabolism of this drug is impaired in subjects with acute hepatitis or cirrhosis, but conflicting data have been reported regarding patients with chronic postinfectious hepatitis or liver cancer. We studied conventional liver-function parameters and antipyrine metabolism (antipyrine per o.s. 18 mg/kg) in 518 subjects. One hundred and one patients had liver metastases (various primaries). Based on the number and size of lesions, the hepatic involvement was considered minimal in 47 and massive in 54 (groups B1 and B2, respectively). One hundred and two had chronic active hepatitis (CAH); 51 patients with histological evidence of fibrosis/early cirrhosis and 51 patients were without histological evidence of fibrosis/early cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control group was composed of 103 subjects with healthy livers (group A). Antipyrine clearance (AP Cl) in CAH patients with fibrosis (0.246 +/- 0.98 mL/min per kg) was similar to that observed in patients with cirrhosis (0.223 +/- 0.148 mL/min per kg), and both values were significantly lower than that found in CAH patients without fibrosis (0.406 +/- 0.159 mL/min per kg, P < 0.01). Antipyrine clearance in patients with liver metastases (0.426 +/- 0.174 mL/min per kg) was similar to that of the healthy group (0.489 +/- 0.210 mL/min per kg). Cirrhotics and cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of impairment. Antipyrine clearance was positively correlated with serum albumin (r2 = 0.10, P = 0.01) and prothrombin time (r2 = 0.129, P < 0.01) in all groups, except those with liver metastases. In patients with CAH, the presence of fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of impairment in groups with liver metastases suggests that the functional hepatic reserve is maintained even in the presence of massive neoplastic invasion.

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“…However, a simplified procedure using a I or 2 samples has been proposed by Dossing et al (1982) and by Williams and Farrell (1989).…”

Section: Discussionmentioning

confidence: 99%

Identification of Patients with Impaired Hepatic Drug Metabolism Using a Limited Sampling Procedure for Estimation of Phenazone (Antipyrine) Pharmacokinetic Parameters

Fabre¹,

Bressolle²,

Goméni³

et al. 1993

Clinical Pharmacokinetics

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Phenazone (antipyrine) 1g was given by short intravenous infusion to 62 study participants (10 healthy drug-free volunteers and 52 patients with chronic liver disease). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of phenazone. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 30 patients. When combined with 1 plasma drug concentration from members of the second group, these led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 32 individuals. Total clearance computed by Bayesian estimation was compared with maximal likelihood estimation of this parameter, the classical procedure. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean error was 0.0477 L/h. The precision of the prediction of this parameter (0.155 L/h) remained lower than the interindividual standard deviation (0.765 L/h). This procedure enables the estimation of individual pharmacokinetic parameters for phenazone. In this study, numerous laboratory tests were performed. A highly significant correlation (p < 0.001) was found between phenazone clearance and the prothrombin time, albumin, gamma-globulin, factor V, antithrombin III, fibrinogen and total bilirubin. Discriminant analysis determined that protein, alkaline phosphatase, creatininaemia and gamma-globulin had more significant discriminating power and gave better prognostic results than those seen with the Child-Pugh test.

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Serial antipyrine clearance studies detect altered hepatic metabolic function during spontaneous and interferon-induced changes in chronic hepatitis B disease activity

Cited by 29 publications

References 41 publications

Clinical significance of the trimethadione tolerance test in chronic hepatitis: A useful indicator of hepatic drug metabolizing capacity

Clinical significance of the trimethadione tolerance test in chronic hepatitis: A useful indicator of hepatic drug metabolizing capacity

Antipyrine clearance in chronic and neoplastic liver diseases: A study of 518 patients

Identification of Patients with Impaired Hepatic Drug Metabolism Using a Limited Sampling Procedure for Estimation of Phenazone (Antipyrine) Pharmacokinetic Parameters

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