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Biomedical subjects

W Zilly

Publications and source records attributed to W Zilly.

At least 55 records · Page 3Linked to original sources
PubMed1978

Influence of corticosteroid on hexobarbital and tolbutamide disposition.

The influence of 10 days' prednisone treatment on the disposition of hexobarbital and tolbutamide was studied in 7 healthy male volunteers. No significant changes in the pharmacokinetic parameters of the two drugs became apparent, which indicates that prednisone pretreatment does not affect their metabolic activities.

Adult↗
PubMed1977

Stimulation of drug metabolism by rifampicin in patients with cirrhosis or cholestasis measured by increased hexobarbital and tolbutamide clearance.

Eleven patients with hepatic cirrhosis or cholestasis were treated with rifampicin for 7 to 132 days. Ten patients received hexobarbital (7.32 mg/kg) and five received tolbutamide (20 mg/kg) by i.v. infusion prior to and after rifampicin treatment; plasma concentrations of the two test compounds were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 624 to 262 min and that of tolbutamide from 292 to 160 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased more than two-fold and that of tolbutamide almost two-fold. The results suggests that rifampicin is able to stimulate hepatic drug metabolism in patients with liver disease. It was apparent in general that the induction did not lead to improvement of hepatocellular function during disease as judged by laboratory findings.

Adult↗
PubMed1977

Influence of rifampicin on drug metabolism: differences between hexobarbital and antipyrine.

Six healthy volunteers were treated with 1,200 mg of rifampicin daily for 8 days. Before and immediately afterward each received indocyanine green, hexobarbital, galactose, and antipyrine by intravenous infusion on 3 consecutive days. The plasma concentrations of the drugs were determined several times after infusion. The average elimination half-life of hexobarbital had decreased from 407 to 171 min and its metabolic clearance had increased almost threefold. In contrast, the average elimination half-life of antipyrine was virtually the same on both occasions (6.9 and 7.2 hr) and there was no change in metabolic clearance. In a tuberculous patient treated with rifampicin the antipyrine elimination rate was unaffected. Rifampicin did not influence indocyanine green clearance or galactose elimination capacity. Serum gamma glutamyl transferase was not affected but urinary D-glucaric acid excretion was increased during rifampicin treatment. The experiment with hexobarbital was repeated after 2 weeks in all subjects; half-lives and clearance values had returned to near control values. It appears that rifampicin is a selective inducer of oxidative drug metabolism in man.

Adult↗
PubMed1977

[Metabolism of hexobarbital in patients with acute hepatitis and cirrhosis (author's transl)].

16 patients with acute hepatitis, 18 patients with cirrhosis and a total of 21 volunteers and patients with normal liver function received 7.32 mg/kg hexobarbital by linear intravenous infusion within 60 min. Hexobarbital was determined gaschromatographically in serial blood samples and the hexobarbital-clearance was calculated from the plasma concentration curve versus time. Additional experiments were performed in rats suffering from so called "galactosamine hepatitis". In half of the patients with acute hepatitis a normal hexobarbital clearance could be found. In the other patients this was distinctly reduced but not correlation was found to other liver function tests. Patients with cirrhosis were subdivided into two groups. The patients in group 1 were well compensated. The patients in group 2 had a decompensated state with ascites and oesophageal varices. In nearly all patients with cirrhosis the hexobarbital-clearance was diminished. This was more pronounced in group 2. Ketohexobarbital excretion in healthy subjects was in the range of 40-60% of dose. Patients with acute hepatitis excreted only 10-20% of dose and patients with liver cirrhosis only about 5% of dose. In rats with "galactosamine hepatitis" hexobarbital clearance in vivo was distinctly reduced and this could be explained by diminished microsomal cytochrome p 45- and hexobarbital oxidation rate.

Acute Disease↗
PubMed1975

Induction of drug metabolism in man after rifampicin treatment measured by increased hexobarbital and tolbutamide clearance.

Five healthy volunteers took 1.2 g rifampicin daily for 8 days, and before and afterwards each received hexobarbital (7.32 mg/kg) and tolbutamide (20 mg/kg) by i.v. infusion on two consecutive days. The plasma concentrations of the two drugs were determined during and after infusion. The average elimination half-life of hexobarbital had decreased from 325 to 122 min and of tolbutamide from 418 to 183 min following rifampicin treatment. It was calculated that the metabolic clearance of hexobarbital had increased about three-fold and that of tolbutamide more than two-fold. Significant changes in the distribution kinetics of the two drugs were not observed. The results suggest that rifampicin is capable of inducing drug metabolism in man, which leads to an increased rate of elimination of drugs that undergo biotransformation in the liver.

Adult↗
PubMed1975

[Cholestatic jaundice after taking the laxative Normolaxol].

Report on two cases of jaundice developing shortly after ingestion of a new laxative, Normolaxol (quinolylmethylenediphenol). Clinical and morphological aspects of the acute cholestasis are described and discussed regarding differential diagnosis and pathogenesis.

Adult↗
PubMed1975

Pharmacokinetics and metabolism of digoxin- and beta-methyl-digoxin-12aplha-3 H in patients with acute hepatitis.

Pharmocokinetics and metabolism of digoxin and beta-methyldigoxin have been studied in patients with acute hepatits after intravenous administration of both H-labeled glycosides. In contrast to digoxin, the rate of decline of radioactivity after administration of beta-methyldigoxin was significantly retarded in patients with acute hepatitis. The increase in plasma concentration after beta-methyldigoxin to patients with acute hepatitis is probably related to decreased demethylation.

Acute Disease↗
PubMed1975

Pharmacokinetics of hexobarbital in acute hepatitis and after apparent recovery.

The pharmacokinetics of hexobarbital were studied in 13 patients with acute hepatitis. Hexobarbital sodium was administered by zero order intravenous (iv) infusion, and plasma concentrations were determined regularly by gas chromatography. For each patient the data were fitted according to 2-compartment kinetics. The results were compared to those obtained for 14 healthy volunteers. The elimination half-life of hexobarbital was 490 +/- 186 min in the hepatitis patients and 261 +/- 69 min in the control group. Clearance was significantly reduced in the hepatitis group, whereas the volume of distribution at steady state was not significantly altered. For some patients the initial distribution volume was reduced. In 6 patients the experiment with hexobarbital was repeated after apparent recovery from hepatitis as judged by normal transaminase and bilirubin levels. Generally the half-life of hexobarbital was shorter and the clearance value was higher than during the acute illness, but the values had not yet returned to normal. Clinical recovery from liver disease is not accompanied by corresponding recovery of drug-metabolizing capability.

Adolescent↗
PubMed1975

Pharmocokinetics of hexobarbital in man after intravenous infusion.

The plasma levels of hexobarbital in humans were determined during and after a 30-min or 60-min zero-order intravenous infusion. Hexobarbital kinetics could be described by conceiving the body to exhibit two compartments. The plasma concentrations were fitted to the postinfusion equation and the parameters intrinsic to the two-compartment open model were estimated. The elimination half-life varied considerably among the 14 individuals (160-441-min), which could mainly be explained by the greatly varying metabolic clearance of the compound (123-360 ml/min). The apparent volume of distribution per kilogram of body weight was relatively constant (1.10 plus or minus 0.12 liters/kg).

Adult↗