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Biomedical subjects

Y Horsmans

Publications and source records attributed to Y Horsmans.

At least 109 records · Page 6Linked to original sources
PubMed1994

D-propoxyphene and norpropoxyphene kinetics after the oral administration of D-propoxyphene: a new approach to liver function?

In an attempt to design a liver function test which takes into account both portal-systemic shunting and hepatocellular dysfunction, we investigated a group of patients with cirrhosis with or without surgical porta-caval shunt for d-propoxyphene and its major metabolite, norpropoxyphene kinetics. A small dose of d-propoxyphene (0.7 mg/kg body weight) was given orally to seven normal subjects, 15 patients with cirrhosis and seven patients with cirrhosis and surgical portacaval shunt. D-propoxyphene and norpropoxyphene areas under the plasma concentration-time from 0 to 4-h (AUC) were determined by the trapezoidal method. As d-propoxyphene is a high extraction drug and since the production of norpropoxyphene should reflect the amount of d-propoxyphene available to the hepatocytes, we tested the hypothesis that norpropoxyphene/d-propoxyphene AUC ratios should reflect both the degree of portal-systemic shunting and the severity of hepatocyte dysfunction. Norpropoxyphene/d-propoxyphene AUC ratios were significantly lower in patients with cirrhosis (mean +/- S.D.: 0.92 +/- 0.59) than in controls (2.51 +/- 0.45) and also significantly lower in patients with cirrhosis and a surgical shunt (0.53 +/- 0.23) than in patients with cirrhosis but without surgical shunt (1.10 +/- 0.63). Moreover, there was an overall statistically significant correlation between norpropoxyphene/d-propoxyphene AUC ratios and branched to aromatic amino acids ratios (rs = 0.91) and fasting venous NH4 (rs = -0.63). On the other hand, there was only a weak correlation between norpropoxyphene/d-propoxyphene AUC ratios and the 14C-aminopyrine breath test (rs = 0.43). These data suggest that the norpropoxyphene/d-propoxyphene AUC ratio reflects both shunting and reduced hepatocellular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Autoimmune chronic active hepatitis responsive to immunosuppressive therapy evolving into a typical primary biliary cirrhosis syndrome: a case report.

The evolution from a characteristic picture of autoimmune chronic hepatitis type I to primary biliary cirrhosis is reported in a middle-aged woman. The initial diagnosis of autoimmune chronic liver disease was based on clinical, bio-serological and histological grounds. It was further confirmed by complete remission following immunosuppressive treatment and prompt relapses at the time of therapy withdrawal. After 7 years, the characteristics of liver disease were altered with increased biochemical cholestasis and serum IgM concentrations, positivation of previously negative anti-M2 antimitochondrial antibodies and the appearance of a typical histological picture of stage I primary biliary cirrhosis. We believe that this is the first reported case in which autoimmune chronic hepatitis highly responsive to immunosuppressive therapy has been followed by the development of a characteristic picture of primary biliary cirrhosis.

Autoimmune Diseases↗
PubMed1994

Possible association between poor metabolism of mephenytoin and hepatotoxicity caused by Atrium, a fixed combination preparation containing phenobarbital, febarbamate and difebarbamate.

Drug hepatotoxicity is partially determined by genetic factors involved in drug metabolism, which may involve the debrisoquine oxidation polymorphism mediated by cytochrome (CYP) 2D6. The purpose of this study was to assess the relationship between drug hepatotoxicity and another genetic polymorphism of drug oxidation, namely that of S-mephenytoin metabolism mediated by CYP2CMP. Mephenytoin hydroxylation capacity was assessed by a hydroxylation index in 24 patients with drug-induced hepatitis and in 23 healthy controls. Hydroxylation index was calculated as the ratio of S-mephenytoin dose to the (0-10 h) urinary excretion of 4-hydroxymephenytoin after oral administration of 100 mg racemic mephenytoin. The test was performed following the patient's recovery. In three patients, hepatitis was related to Atrium, a drug containing phenobarbital, febarbamate and difebarbamate. The mean hydroxylation index (+/- SD) value in patients with Atrium hepatitis (12.4 +/- 8.3) was markedly higher than that found in healthy controls (1.8 +/- 0.4) or in patients with other drug-induced hepatitis (2.5 +/- 3.3). Mean hydroxylation index values were similar in the two latter groups. Considered individually, oxidation capacity was low (hydroxylation index > 9) in two of the three patients with Atrium hepatitis and intermediate (hydroxylation index between 4 and 9) in the third patient. In contrast, all 23 healthy subjects exhibited a high oxidation capacity (hydroxylation index < 4). In the 21 patients with other drug-induced hepatitis, oxidation capacity was high in 19 subjects, intermediate in one subject with chlorpromazine hepatitis, and low in one subject with dapsone hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Short report: interferon-alpha decreases 14C-aminopyrine breath test values in patients with chronic hepatitis C.

OBJECTIVE: To investigate the effect of interferon-alpha on cytochrome P-450 dependent microsomal function. METHODS: The 14C-aminopyrine breath test was performed before, during and after a standard dose of interferon-alpha (3,000,000 units three times per week) was administered for at least six months (nine patients with chronic hepatitis C). RESULTS: Mean aminopyrine breath test values obtained during therapy were significantly lower than either pre- or post-treatment, the degree of reduction varying widely between individuals. Pre- and post-treatment aminopyrine breath test values did not differ significantly. CONCLUSION: Interferon therapy is associated with a significant and transient inhibition of cytochrome P-450 activity, which should be taken into account when prescribing concurrent therapy with drugs metabolized by this pathway.

Adult↗
PubMed1994

Biliary cystadenoma of the liver with elevated CA 19-9.

A case of intrahepatic biliary cystadenoma with mesenchymal stroma is reported. The tumor was associated with strikingly elevated serum and intracystic levels of the tumor-associated antigen CA19-9. Two months after surgical enucleation, serum CA 19-9 levels returned to normal.

Adenoma, Bile Duct↗
PubMed1993

Single-dose pharmacokinetics of cetirizine in patients with chronic liver disease.

The pharmacokinetics of the H1-receptor antagonist cetirizine were studied from 0 to 72 hours after a single dose of 20 mg in 5 patients with chronic hepatocellular liver disease (group A), in 5 patients with chronic cholestatic liver disease (group B), and in 16 healthy volunteers. The renal function of patients and volunteers was normal (creatinine clearance > or = 70 mL/min). Cetirizine pharmacokinetics were similar in the two groups of patients. The elimination t1/2 was prolonged in patients (mean +/- standard deviation; group A: 14.32 +/- 2.30 hours; group B: 13.86 +/- 3.14 hours) in comparison with the values observed in volunteers (9.42 +/- 2.4 hours). A reduced apparent oral body clearance also was observed in patients (group A: .48 +/- .23 mL/min/kg; group B: .41 +/- .09 mL/min/kg) in comparison with volunteers (.74 +/- .19 mL/min/kg). No differences were observed in the mean cumulative urinary excretion between patients (group A: 69 +/- 15%; group B: 69 +/- 13%) and volunteers (70.7 +/- 7.8%).

Adult↗
PubMed1993

Hepatic [14C]aminopyrine demethylation capacity after portocaval shunting. Comparative study in patients with and without arterialization of portal vein.

The [14C]aminopyrine breath test (ABT) was used before and after surgical portocaval shunting in 29 cirrhotic patients, 15 with arterialization of the portal vein and 14 without. These two subgroups were comparable with regard to age, prothrombin time, serum albumin, serum total bilirubin concentrations, Child classification, and preoperative ABT. After portocaval shunt, a striking reduction in ABT values was observed after 6 and 12 months (90.7 +/- 8.0%, P < 0.05 and 77.3 +/- 7.5%, P < 0.005, respectively). No further decrease was observed between 12 and 24 months. The microsomal function was reduced to a greater extent in patients with postnecrotic cirrhosis (55 +/- 4.8%, P < 0.01) than in those with alcoholic cirrhosis (84.8 +/- 10.4%, P < 0.05). Arterialization of the portal stump of the portal vein did not prevent the reduction in hepatocellular function. No significant change in prothrombin time, serum albumin, or bilirubin concentrations was observed during the follow-up period in any of the groups. Overall, preoperative ABT was significantly higher in those surviving one year (0.29 +/- 0.12% administered dose) than in those who died within this time period (0.12 +/- 0.01%, P < 0.005). This observation suggests that portocaval anastomosis induces an early decrease in microsomal function that is not prevented by arterialization of the portal vein. It also suggests that ABT might be helpful in selecting patients for shunt surgery.

Adult↗
PubMed1993

Scoparone O-demethylase assay is not useful to differentiate the effects of model inducers of cytochrome P-450 in rabbit and guinea pig liver.

Coumarin derivative, scoparone (6,7-dimethoxycoumarin), is regioselectively O-demethylated into isoscopoletin (I) and scopoletin (S). This oxidation is inversely influenced by cytochrome P-450 inducers in the rat such as 3-methylcholantrene (3-MC) and phenobarbital (PB). The I/S ratio is higher than 1.5 with 3-MC treatment whereas it is lower than 0.5 with PB treatment. With regards to this contrasting effect, it has been suggested that the I/S ratio should be useful to differentiate between the effects of these types of inducers. We studied the consequences of in vivo PB and 3-MC treatment on scoparone biotransformation in guinea pig and rabbit. In these two species, at the basal state, scoparone biotransformation was enhanced in comparison to the rat. Moreover, in these untreated animals, two other metabolites were formed. After 3-MC or PB treatment, scoparone metabolism is, in contrast to the rat, inappropriate to differentiate between the P-450 profile of other animals.

Animals↗
PubMed1993

A pharmacokinetic evaluation of the second-generation H1-receptor antagonist cetirizine in very young children.

The pharmacokinetics of the second-generation H1-receptor antagonist cetirizine was studied in eight children younger than 4 years of age who were treated with a single dose of cetirizine solution (5 mg). These children were hospitalized with suspected allergic respiratory problems or recurrent respiratory tract infections. Blood samples were collected at 1/2, 1, 1 1/2, 2, 4, 6, 8, 12, and 24 hours, and a 24-hour urine collection was performed in five of the samples. The findings obtained in children were compared with those obtained in 16 healthy young adults (mean +/- SD, 24.6 +/- 4.1 years) who received a single 20 mg dose. Cetirizine was absorbed more slowly in children (p = 0.006; mean +/- SD, 1.44 +/- 1.12 hours) than in adults (0.62 +/- 0.22 hours). The plasma elimination half-life of cetirizine was significantly shorter in children (p < 0.001; 4.91 +/- 0.6 hours) than in adults (8.6 +/- 2.1 hours), and the clearance rate was significantly higher in children (p < 0.001; 1.48 +/- 0.41 ml/min/kg) than in adults (0.80 +/- 0.17 ml/min/kg). Urinary excretion of unchanged cetirizine was significantly lower in children (p < 0.001; 37.8% +/- 5.2%; n = 5) than in adults (57.7% +/- 11.8%). Therefore the metabolism of cetirizine is faster in young children than in adults. This effect must be taken into account in future pharmacodynamic studies in this age group.

Absorption↗
PubMed1992

Effects of combined bezafibrate-simvastatin appraised in healthy subjects.

The occurrence of clinical and biochemical side effects of bezafibrate (400 mg daily) or simvastatin (20 mg daily) alone or combined was appraised in 13 healthy male normolipidemic subjects according to a single blind design. Each period of 2 weeks of treatment with bezafibrate or simvastatin or bezafibrate plus simvastatin was followed by a period of placebo (1 week). No subjects experienced myalgia or muscle weakness. Plasma creatine kinase (CK) elevations, particularly skeletal muscle CK (CK-MM), were observed in 6 subjects: 11 times during different placebo periods, 5 times on bezafibrate, 4 times on simvastatin, and 4 times on combined bezafibrate-simvastatin, but never reached 1,600 IU/L. Only a trend to an increase of CK mean values on combined bezafibrate-simvastatin was shown. The hepatic transaminase and gamma-glutamyltransferase activities remained unmodified throughout the trial, unlike alkaline phosphatase activity, which fell on bezafibrate and on bezafibrate plus simvastatin. The low-density lipoprotein cholesterol level was more reduced with simvastatin than with bezafibrate. The addition of bezafibrate to simvastatin did not decrease it further. Lecithin:cholesterol acyltransferase activity expressed as fractional esterification rate was enhanced only on simvastatin and bezafibrate-simvastatin.

Adult↗
PubMed1992

Immunoquantification of cytochrome P-450 3A on rat paraffin-embedded liver tissue.

The cytochrome P-450 3A family is involved in the metabolism of several drugs, including nifedipine, cyclosporine, quinidine and erythromycin. The purpose of this study was to develop a reliable method to obtain a relative quantification of cytochrome P-450 3A apoproteins in rat liver specimens by immunocytochemistry and to correlate such quantification to erythromycin N-demethylase activity, a biochemical pathway sustained by that enzymatic system. Thirty-six male Wistar rats were treated with an injection of either saline or dexamethasone phosphate (10, 30 or 50 mg/kg), a potent inducer of cytochrome P-450 3A. Specimens taken from the same lobe were processed for immunocytochemistry and determination of erythromycin N-demethylase activity. Paraffin sections were treated with a polyclonal antiserum directed against cytochrome P-450 3A. The density of cytochrome P-450 3A immunostaining measured by an automatic image analyzer increased with the dose of dexamethasone pretreatment, and with the erythromycin N-demethylase activity, both parameters being closely correlated. Our data indicate that in rats, when cytochrome P-450 3A is concerned, there is a close correlation between the results of immunoquantitation and biochemical activity. This suggests that such a method of investigation might be used on small paraffin-embedded liver specimens obtained by needle biopsy.

Animals↗