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PubMedDate not supplied

Antipyrine metabolism in patients with diabetes mellitus.

1. A pharmacokinetic study of antipyrine was performed in healthy volunteers and diabetic subjects, ten in each group. After a single oral dose of antipyrine (18 mg/kg) multiple samples of saliva were collected for the determination of antipyrine concentration and a pharmacokinetic analysis was carried out. 2. The mean salivary half-life of antipyrine was found to be significantly higher in patients with uncontrolled diabetes as compared to the healthy subjects. However, there was no significant difference in volume of distribution and metabolic clearance rates. 3. After 15 days of insulin therapy, there was a significant reduction in the mean half-life of antipyrine in the diabetic patients. The mean half-life of antipyrine in the patients with controlled diabetes was not significantly different from that of the normal healthy subjects. 4. There was no significant correlation between the salivary half-life of antipyrine and a 2 hour postprandial blood sugar level in the diabetic patients. 5. Our data suggest impaired hepatic microsomal enzyme activity in patients with uncontrolled diabetes which was corrected after 15 days of insulin therapy.

Adult↗
PubMed1998

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

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.

Adolescent↗
PubMed2002

The concordance of early antipyrine and thiopental distribution kinetics.

Studies of factors affecting the initial disposition of drugs with a rapid onset of effect following i.v. administration have used antipyrine as a surrogate for lipophilic drugs because it lacks cardiovascular effects. The present study tested the assumption that antipyrine is a useful surrogate for the flow-dependent tissue distribution of the lipophilic drug thiopental by comparing the recirculatory pharmacokinetic models of antipyrine and thiopental disposition after concomitant administration to five dogs anesthetized with 1.5% halothane. The pharmacokinetics of indocyanine green, a marker of the intravascular behavior of antipyrine and thiopental, and antipyrine in these dogs was nearly identical to that described previously in dogs anesthetized with 1.5% halothane but not given thiopental. The total volume of distribution of the highly lipophilic drug thiopental was more than 60% larger than that of antipyrine, 53 versus 33 liters, respectively. Nonetheless, the initial distribution kinetics of the two drugs, including the pulmonary tissue volume and the volume of the nondistributive pathway as well as the clearance to it, were nearly identical. As a result, the fraction of cardiac output involved in distribution of the two drugs to peripheral tissues was similarly identical, although the distribution of cardiac output between clearance to the rapidly equilibrating tissues and clearance to the slowly equilibrating tissues differed slightly. This study validates the assumption that antipyrine is a useful surrogate for lipophilic drugs in pharmacokinetic studies in which physiologic stability is desirable to meet the assumption of system stationarity.

Animals↗
PubMed1978

Impairment of antipyrine clearance in humans by propranolol.

The effect of propranolol on antipyrine clearance in humans was evaluated in six healthy volunteers who received single 1.4 to 1.5 g doses of intravenous antipyrine on two occasions. The first (control) antipyrine trial was without concurrent drug administration; the second trial was done during treatment with therapeutic doses of propranolol (40 mg every 4 to 6 hours). Antipyrine elimination half-life (t1/2), volume of distribution (Vd), and total clearance were determined after each trial. In all subjects isoproterenol sensitivity decreased markedly during propranolol treatment, indicating a high degree of beta blockade produced by the drug. Mean antipyrine t1/2 during the propranolol treatment period was significantly prolonged, and total clearance significantly reduced, over the control values. Twenty-four-hour urinary excretion of 4-hydroxyantipyrine, the major metabolite of antipyrine, likewise was reduced from 23.6% of the dose on the control trial to 14.8% of the dose during propranolol coadministration (0.1 less than P less than 0.2). Vd however, was nearly identical during both trials (0.62 L/kg). Thus propranolol prolongs the half-life and reduces the clearance or biotransformation rate of antipyrine, a drug whose clearance is independent of hepatic blood flow. Propranolol may influence the activity of hepatic microsomal enzymes responsible for drug hydroxylation.

Adult↗
PubMed2000

Evaluation of the influence of diabetes mellitus on antipyrine metabolism and CYP1A2 and CYP2D6 activity.

STUDY OBJECTIVE: To evaluate the metabolism of antipyrine, a general metabolic probe, caffeine, a probe for cytochrome P450 (CYP) 1A2 and N-acetyltransferase activity, and dextromethorphan, a specific probe for CYP2D6 activity in patients with type 1 or 2 diabetes mellitus. DESIGN: Prospective, controlled study. SETTING: Research facility. Patients. Fifteen patients with type 1 and 16 with type 2 diabetes, and 16 healthy controls. INTERVENTION: Each subject simultaneously received antipyrine 10 mg/kg, caffeine 100 mg, and dextromethorphan 30 mg. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of antipyrine and its primary metabolites were determined from saliva and urine samples. Type 1 diabetes had marked effects on antipyrine metabolism whereas type 2 disease did not alter the metabolism of any of the probe drugs. The apparent oral clearance of antipyrine was increased 72% in patients with type 1 disease compared with controls (p=0.0001). In addition, formation clearances of 4-hydroxyantipyrine and 3-hydroxymethylantipyrine were increased by 74% and 137% in those patients relative to controls. The caffeine metabolic index (paraxanthine/caffeine) was increased 34% (p=0.11), and N-acetylation and CYP2D6 phenotype were not altered. CONCLUSION: The metabolism of antipyrine is increased in patients with type 1 diabetes. Based on in vitro reports of antipyrine metabolism and current caffeine metabolic index data, the predominant effect of type 1 diabetes appears to be an increase in CYP1A2 activity. Assessment of the effect of the disease on other specific CYP metabolic pathways is warranted.

Acetylation↗
PubMed1985

Isolation and characterization of the four antipyrine glucuronides and determination of their urinary excretion pattern in man by a reversed-phase h.p.l.c. assay.

A large-scale procedure for the isolation of four urinary glucuronides in antipyrine metabolism is described; the isolated compounds are used as standards in a direct h.p.l.c. assay. The four glucuronides were characterized by u.v. and 1H-n.m.r. spectroscopy, and after hydrolysis by a t.l.c. assay of the corresponding aglycones. A reversed-phase h.p.l.c. assay procedure has been developed for the direct quantification of the four antipyrine glucuronides; this separates 3-hydroxymethyl-antipyrine glucuronide, 4,4'-dihydroxy-antipyrine glucuronide, norantipyrine glucuronide and 4-hydroxy-antipyrine glucuronide in a single run. Urinary elimination patterns of these glucuronides have been determined in five female and five male volunteers after antipyrine (1200 mg) administration. The direct assay of urinary glucuronides enables the simultaneous determination of glucuronidation activities and four different phase-I metabolites of antipyrine in vivo.

Adult↗
PubMed1999

Direct detection of antipyrine metabolites in rat urine by (13)C labeling and NMR spectroscopy.

Antipyrine is a useful probe to evaluate variation of in vivo activities of oxidative hepatic drug-metabolizing enzymes. Here we describe a new approach using (13)C labeling and NMR spectroscopy for the direct and simultaneous detection of all phase I and phase II metabolites of antipyrine in rat urine. [C-methyl-(13)C]Antipyrine was synthesized and administered orally to rats (100 mg/kg), and the 0- to 24-h postdose urine was analyzed by 100-MHz (13)C NMR spectroscopy under the conditions of distortionless enhancement by polarization transfer without any pretreatments such as deconjugation, chromatographic separation, and solvent extraction. Consequently, all the major metabolites in urine were successfully detected with favorable signal-to-noise ratios in the limited acquisition time (30 min). The assignments of the resonances were performed by enzymic modification and spiking authentic samples. The reproducibility of the NMR detection was sufficient for the quantitative evaluation of the metabolic profile. Effects of 3-methylcholanthrene on antipyrine metabolism were examined by this approach to evaluate variation of in vivo phase I and phase II metabolism of antipyrine in rats. The present approach is useful and practical to evaluate variation of in vivo activities of conjugation enzymes as well as oxidation enzymes responsible for the formation of antipyrine metabolites in rats. This direct approach would enhance the value of the antipyrine test because of the simplicity and convenience.

Animals↗
PubMed1999

Estimation of functional liver reserve in patients before cardiac surgery using antipyrine plasma clearance test.

BACKGROUND: Hyperbilirubinemia is not uncommon and is sometimes fatal after valvular surgery. One important cause of it is a poor functional liver reserve, however, conventional tests reflect hepatic blood flow and do not offer precise evaluation of the pure functional liver reserve. Antipyrine has particular pharmacological properties, and its plasma clearance represents quantitatively the functional capacity of the liver. In this study, we measured antipyrine plasma clearance in cardiac surgical patients and evaluated the feasibility of using this parameter as a predictor of the risk of postoperative hyperbilirubinemia. METHODS: The plasma clearance of antipyrine was measured preoperatively in 40 cardiac patients undergoing mitral and/or tricuspid valvular surgery and its relations with hemodynamics or postoperative course were studied. RESULTS: Antipyrine clearance in preoperative patients was 0.365+/-0.175 (mean +/- SD) ml/min/kg, lower than the normal range (0.405+/-0.04 ml/min/kg), and showed no correlation with cardiac index, while the plasma disappearance rate of indocyanine green depended on the cardiac index. The maximum postoperative total bilirubin level showed significant correlation with antipyrine clearance (r=-0.699); this correlation coefficient was greater than that with indocyanine green (-0.477). The correlation was more prominent in patients with cardiac dysfunction. Furthermore, antipyrine clearance showed significant predictability of the duration of ICU stay. CONCLUSIONS: Antipyrine clearance provides a precise estimate of functional liver reserve which is independent of hemodynamics and predicts the risk of postoperative hyperbilirubinemia in preoperative cardiac patients.

Adult↗
PubMed1988

The effect of antipyrine and rifampicin on the excretion of renal enzymes in human urine.

Two well-known drugs that induce the liver microsomal enzyme system in man were administered to 3 different groups of healthy male volunteers. Antipyrine 1200 mg and rifampicin in two different doses of 600 mg or 1200 mg daily were given orally to each group over a period of seven days. The extent of liver microsomal enzyme induction was assessed by estimating antipyrine elimination, serum gamma-glutamyl-transferase (GGT) activity and the urinary excretion rate of 6-beta-hydroxycortisol. In addition, possible effects on renal enzymes were monitored by measuring gamma-glutamyltransferase (GGT) and beta-glucuronidase (GRS) urinary excretion rates before and after drug administration. The possibility of a direct toxic effect on the renal tubular epithelium following drug administration was assessed by the measurement of urinary beta-N-acetylglucosaminidase (AGS) activity, total protein and glucose. Antipyrine plasma clearance and 6-beta-OHF excretion rates increased significantly in the groups treated with antipyrine or rifampicin, while serum GGT activities were enhanced only following antipyrine. Antipyrine administration increased urinary GGT excretion both immediately and one week after cessation of drug administration, but no changes were found following the administration of rifampicin. GRS, AGS, total protein and glucose excretion in urine remained unchanged during and after the administration of each individual drug. Based on these findings, the increased urinary GGT excretion observed following antipyrine treatment may be due to an inducing effect on the renal tubular cells, as no evidence for a toxic renal damage was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Substrate-selective inhibition by verapamil and diltiazem: differential disposition of antipyrine and theophylline in humans.

Antipyrine and theophylline disposition was studied in healthy volunteer subjects in the control state while the subjects were taking verapamil (120 mg) orally four times daily or diltiazem (120 mg) orally three times daily. Both verapamil and diltiazem treatment decreased antipyrine clearance (verapamil, 42.5 to 30.1 ml/min, P less than .01; diltiazem, 41.7 to 29.9 ml/min, P less than .01), resulting in prolonged antipyrine half-life with no change in distribution volume. Fractional clearances of urinary antipyrine metabolites 4-hydroxyantipyrine, 3-hydroxymethylantipyrine, norantipyrine and unchanged antipyrine were differentially changed by verapamil and diltiazem treatment. With verapamil treatment, 4-hydroxyantipyrine and norantipyrine fractional clearances were markedly decreased, with 3-hydroxymethylantipyrine slightly decreased and antipyrine unchanged. With diltiazem treatment, 3-hydroxymethylantipyrine was decreased, with no significant change in 4-hydroxyantipyrine, norantipyrine or antipyrine. Effect on theophylline clearance differed between verapamil treatment (57.7 to 44.7 ml/min; P less than .01) and diltiazem treatment (50.2 to 49.4 ml/min; N.S.), with prolonged theophylline half-life during verapamil treatment, no change in half-life during diltiazem treatment and distribution volume unchanged by either treatment. Fractional clearances of urinary theophylline metabolites 3-methylxanthine, 1-methyluricacid, 1,3-dimethyluricacid and unchanged theophylline reflected the differential plasma theophylline clearance. During verapamil treatment, 3-methylxanthine and 1,3-dimethyluricacid fractional clearances were decreased, with no change in 1-methyluricacid or theophylline. During diltiazem treatment, 1,3-dimethyluricacid fractional clearance was slightly decreased, and 3-methylxanthine, 1-methyluricacid and theophylline were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1978

Microsomal enzymes in patients with gastric carcinoma as determined by plasma half-life of antipyrine.

Metabolism of antipyrine was studied in 12 patients with gastric carcinoma and 5 control subjects with peptic ulcer matched for sex, body weight, height, and smoking history. The mean antipyrine half-life was significantly longer (21.5 +/- 1.5 hr) in 3 patients with disseminated gastric carcinoma compared to control subjects (9.3 +/- 1.5 hr) (P less than 0.001). There was no significant difference in the mean antipyrine half-life between 9 patients with localized gastric carcinoma and control subjects. Similarily, the mean metabolic clearance rate of antipyrine was significantly lower (22.8 +/- 5.0 ml/hr/kg) in patients with disseminated gastric carcinoma compared to control subjects (52.6 +/- 13.4 ml/hr/kg) (P less than 0.02). Thus, the presence of gastric carcinoma in humans might alter antipyrine elimination. Significant negative correlation was observed between antipyrine half-life and albumin concentration (r = -0.786, P less than 0.01). These observations indicate that the decrease in antipyrine half-life is not primarily due to the presence of tumor but rather to the nutritional status of an individual.

Antipyrine↗
PubMed1994

Antipyrine and caffeine dispositions in clinically normal dogs and dogs with progressive liver disease.

Dispositions of caffeine and antipyrine were compared as indicators of decreasing hepatic function in dogs with experimentally induced progressive liver disease. Dimethylnitrosamine, a hepatospecific toxin, was administered orally to 16 dogs; 6 dogs served as controls (group 1). Three classes of liver disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of antipyrine, and 24 hours later, caffeine was studied 3 weeks after the last dose of toxin in each dog. For both drugs, rapid IV administration of 20 mg/kg of body weight was administered and serum samples were obtained at intervals for determination of at least 5 terminal-phase drug half-lives. For both drugs, clearance and mean residence time differed among groups (P < or = 0.01). Clearance of antipyrine and caffeine was decreased in groups 3 and 4, compared with groups 1 and 2. Antipyrine and caffeine mean residence times were longer in group-3 dogs, compared with dogs of groups 1 and 2. Correction of caffeine and antipyrine clearances for hepatic weight increased discrimination between groups 3 and 4. The clearance and mean residence time ratios of antipyrine to caffeine were calculated for each group and, when compared with values for group-1 dogs, were used to test for differences between the 2 drugs in response to disease. Ratios did not differ among groups. These results indicate that the disposition of antipyrine and caffeine may change similarly with progression of dimethylnitrosamine-induced liver disease.

Analysis of Variance↗
PubMed1994

A recirculatory pharmacokinetic model describing the circulatory mixing, tissue distribution and elimination of antipyrine in dogs.

A model of antipyrine disposition from the moment of its injection was developed incorporating the intravascular mixing component as determined by indocyanine green (ICG) kinetics. The simultaneous dispositions of antipyrine and ICG were characterized in five dogs anesthetized with halothane. After injecting antipyrine and ICG into the right atrium, femoral arterial blood samples were collected every 3 sec for the 1st min and less frequently to 20 min for ICG and to 360 min for antipyrine. ICG and antipyrine concentrations were measured by high-performance liquid chromatography and modeled with SAAM 30.1. A fully identifiable recirculatory compartmental model, incorporating the ICG recirculatory model with blood flows and time delays, was used to describe antipyrine disposition. Four distinct antipyrine pharmacokinetic tissue compartments and the distribution clearances assigned to them could be estimated: a pulmonary tissue (0.13 +/- 0.05 I, and 2.51 +/- 0.39 liters/min), a very fast equilibrating tissue (0.12 +/- 0.08 I, and 1.33 +/- 0.22 liters/min), a fast equilibrating tissue (3.21 +/- 0.45 I, and 0.74 +/- 0.09 liters/min) and a slow equilibrating tissue (15.94 +/- 1.8 I, and 0.44 +/- 0.13 liters/min). Although this recirculatory model retains the predominant attributes of traditional pharmacokinetic models, it also can describe completely drug concentrations during the mixing transient when many drugs reach peak effect as well as ascertain the role of cardiac output and its distribution in drug disposition.

Animals↗
PubMed1998

Changes of antipyrine pharmacokinetics during influenza and after administration of interferon-alpha and -beta.

OBJECTIVE: During viral infections serum levels of interferons are elevated. In this study we wanted to observe the effects of endogenous interferon (IFN) during an acute viral infection (influenza) and after external application of interferons on the pharmacokinetics of antipyrine which is a parameter of hepatic cytochrome P450 enzyme activity. METHODS: Endogenous plasma levels of interferons and the antipyrine pharmacokinetics in 10 otherwise healthy volunteers were investigated before outbreak and in the symptomatic interval of an acute viral respiratory infection. The serum interferon levels were determined by RIA. In another trial 2 groups of 9 HIV patients each in stage CDC/WHO B2/3 received low-dose interferon therapy with 0,75 Mio. I.U. interferon-alpha or -beta s.c./die. The concentrations of antipyrine in serum were measured by HPLC. The antipyrine kinetics were determined before the infection or the interferon therapy, respectively, and during viral infection or during interferon or after interferon therapy, respectively. RESULTS: The plasma levels of IFNalpha and IFNgamma were significantly elevated from 4.7 U/ml to 12.6 U/ml and 0.3 U/ml to 3.4 U/ml, respectively, whereas the antipyrine clearance showed a decrease from 57.9 ml/min to 45 ml/min in the symptomatic interval of an acute viral infection. During therapy with low-dose interferons we observed a significant difference after 12 week treatment with IFNalpha or IFNbeta, respectively. In the first group we observed a decreased antipyrine clearance from 49.0 ml/min to 41.7 ml/min; in the second group the antipyrine clearance decreased from 49.0 ml/min to 41.7 ml/min. CONCLUSION: Viral infections (influenza) are able to inhibit the hepatic monooxygenase system due to elevated serum interferon levels. Low doses of exogenous interferons inhibit the cytochrome P450 monooxygenase system.

Adult↗
PubMed1995

The Effects of Lansoprazole on the Disposition of Antipyrine and Indocyanine Green in Normal Human Subjects.

This study was designed to evaluate the potential effects of acute and chronic daily oral doses of lansoprazole (60 mg) on the disposition of antipyrine, an almost completely metabolized low hepatic extraction compound, and indocyanine green, a hepatically secreted compound with high extraction ratio. The study utilized a randomized, placebo-controlled, double-blind, two-period crossover design. Sixteen of 18 subjects completed all phases of the study. Both antipyrine (10 mg kg(minus sign1)) and indocyanine green (0.5 mg kg(minus sign1)) were administered as single intravenous bolus doses on Days 1 and 7 of lansoprazole or placebo dosing. Acute exposure to lansoprazole had no statistically significant effects on the plasma pharmacokinetics of indocyanine green or antipyrine. After the seventh dose, there was a small but statistically significant reductions in indocyanine green total body clearance (CL), and elimination rate constant of 10.6% and 8%, respectively. Additionally, a small statistically significant reduction (8.6%) in antipyrine volume of distribution was detected. No other plasma antipyrine pharmacokinetic parameters were changed with concomitant lansoprazole administration. About a 12% increase in the recovery of one of the major antipyrine urine metabolites (NORA) was detected. Overall, this study demonstrates little or no effect of lansoprazole on the pharmacokinetics of antipyrine and indocyanine green.

Journal Article↗
PubMedDate not supplied

Effects of phenobarbital steady state levels on antipyrine clearance and distribution in the rat.

A group of 15 rats received two intravenous bolus doses of antipyrine (15 mg/kg) separated by a 57 hour infusion (with bolus dose) of phenobarbital. Phenobarbital bolus doses and infusion rates were based on a preliminary pharmacokinetic study (7 rats) and were varied to achieve a broad range of steady state levels. Antipyrine and phenobarbital blood levels were measured by high pressure liquid chromatography. Antipyrine kinetics obeyed first order monoexponential decay, and the parameters (clearance, volume, half-life) were determined. Antipyrine clearance increased in all animals during phenobarbital infusions with a per cent increase ranging between 54.6 and 269 per cent. However, no significant correlation was found between the per cent increase in antipyrine clearance and phenobarbital concentration (r = 0.19). The volume of distribution of antipyrine increased in 14 of 15 animals with increases ranging between 7.7 and 45.8 per cent.

Animals↗
PubMed1979

Metabolism of drugs and carcinogens in man: antipyrine elimination as an indicator.

The suitability of the most commonly used "prototype" drug, viz, antipyrine, in predicting drug and carcinogen metabolism was evaluated, by studying in vivo antipyrine elimination rate (Ke) and in vitro metabolism of drugs and carcinogens in liver preparations in the same individuals. Our subjects were 20 adult males undergoing abdominal surgery for gastrojejunostomy, although antipyrine Ke could be studied in only 16 subjects. Correlations of the various in vito--in vivo parameters were positive between the parameter pairs: in vivo antipyrine Ke--in vitro benzopyrene hydroxylase; benzopyrene hydroxylase--aniline hydroxylase; and benzopyrene hydroxylase--gamma-glutamyl transferase. Aminopyrine demethylase did not correlate with any of the parameters studied. The degree of correlation between antipyrine Ke and benzopyrene hydroxylase was statistically significant but was not satisfactory for predictive purposes. Our study indicates some of the problems and limitations of in vivo--in vitro comparisons and confirms earlier doubts on the usefulness of antipyrine as a "prototype" drug for predicting drug and carcinogen metabolism in man.

Adult↗
PubMed1989

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

The present study was performed to establish whether sequential determinations of antipyrine clearance, using a simplified two-point test, are sensitive and specific indicators of changes in chronic hepatitis B disease activity. Sixteen patients were studied on four or more occasions during 18 to 30 months. Eleven patients were treated with recombinant human alpha-interferon (2.5, 5.0 or 10 X 10(6) per m2, intramuscularly, three times per week, for 24 weeks), and five patients were untreated controls. Among seven patients, (six interferon-treated and one control) who lost hepatitis B e antigen from serum, antipyrine clearance improved by 46% (range: 20 to 160%) from 0.37 +/- 0.14 ml per kg per min (mean +/- S.D.) to 0.54 +/- 0.13 ml per kg per min, p less than 0.005. This change paralleled the loss of symptoms and reduction of serum ALT levels (from 206 +/- 189 IU per liter (mean +/- S.D.) to 38 +/- 12 IU per liter, p less than 0.005). Conversely, antipyrine clearance declined to previous levels when reactivation of chronic hepatitis B with reappearance of HBeAg in serum occurred. Regardless of changes in hepatitis B serology, when serum ALT values fluctuated by more than 20% (presumed to reflect fluctuations in necroinflammatory activity of the liver disease), antipyrine clearance also changed whereas serum albumin and bilirubin concentrations and prothrombin time did not. It is concluded that antipyrine clearance is a more sensitive and specific parameter than conventional indices for assessing hepatic metabolic function during changes in chronic hepatitis B disease activity. Remission in disease with loss of HBeAg from serum is associated with improved hepatic metabolic function as determined by the antipyrine clearance test.

Adult↗